Fungicidal heterocyclic amines

ABSTRACT

Disclosed are compounds of Formula 1, N-oxides, and salts thereof, 
                         
wherein
         R 1 , R 2 , R 9a , R 9b , G, W, X, Y, and Z are as defined in the disclosure.       

     Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

FIELD OF THE INVENTION

This invention relates to certain amines, their N-oxides, salts andcompositions, and methods of their use as fungicides.

BACKGROUND OF THE INVENTION

The control of plant diseases caused by fungal plant pathogens isextremely important in achieving high crop efficiency. Plant diseasedamage to ornamental, vegetable, field, cereal, and fruit crops cancause significant reduction in productivity and thereby result inincreased costs to the consumer. Many products are commerciallyavailable for these purposes, but the need continues for new compoundswhich are more effective, less costly, less toxic, environmentally saferor have different sites of action.

Certain N-phenyl amines have been previously described. World PatentPublication WO 05/033095 discloses amine derivatives of Formula i asfungicides

wherein, inter alia, each of R¹, R², R³, R⁴, R⁵, R⁸, R⁹ and R¹⁰ areindependently H, halogen or alkyl; and each of R⁶, R⁷ and R¹¹ areindependently H or alkyl. World Patent Publication WO 04/084634discloses amine derivatives of Formula ii as fungicides

wherein, inter alia, A and A′ are both N or A and A′ are both CH or A isCH and A′ is N; each of R3, R4, R5 and R6 are independently H, halogenor alkyl; R2 is H or alkyl; and R1 is hydrazino or optionallysubstituted amino. World Patent Publication WO 01/93682 discloses aminederivatives of Formula iii as fungicides

wherein, inter alia, each of R₁, R₂, R₃, R₄ and R₅ are independently H,halogen or alkyl; and R₆ is hydrazino or optionally substituted amino.

The amines of the present invention are not disclosed in thesepublications.

SUMMARY OF THE INVENTION

This invention is directed to compounds of Formula 1 (including allgeometric and stereoisomers), N-oxides, and salts thereof, agriculturalcompositions containing them and their use as fungicides:

wherein

-   -   R¹ is H, halogen, cyano, hydroxy, amino, nitro, —CHO or        —C(═O)NH₂; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₂-C₈        alkylcarbonyl, C₂-C₈ alkoxycarbonyl, C₂-C₈ alkylaminocarbonyl,        C₃-C₁₀ dialkylaminocarbonyl, C₁-C₆ alkoxy, C₃-C₈ cycloalkoxy,        C₂-C₈ alkylcarbonyloxy, C₄-C₁₀ cycloalkylcarbonyloxy, C₁-C₆        alkylthio, C₃-C₈ cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆        alkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₈        dialkylamino, C₃-C₈ cycloalkylamino, C₂-C₈ alkylcarbonylamino,        C₁-C₆ alkylsulfonylamino, G^(A), G^(N) or naphthalenyl, each        optionally substituted with one or more substituents selected        from the group consisting of halogen, cyano, hydroxy, amino,        nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl,        C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₈ alkylcarbonyl, C₂-C₈        haloalkylcarbonyl, C₄-C₁₀ cycloalkylcarbonyl, C₂-C₈        alkoxycarbonyl, C₄-C₁₀ cycloalkoxycarbonyl, C₂-C₈        alkylaminocarbonyl, C₃-C₁₀ dialkylaminocarbonyl, C₄-C₁₀        cycloalkylaminocarbonyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₈        cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy,        C₂-C₆ alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆ alkynyloxy, C₃-C₆        haloalkynyloxy, C₂-C₈ alkoxyalkoxy, C₂-C₈ alkylcarbonyloxy,        C₂-C₈ haloalkylcarbonyloxy, C₄-C₁₀ cycloalkylcarbonyloxy, C₁-C₆        alkylthio, C₁-C₆ haloalkylthio, C₃-C₈ cycloalkylthio, C₁-C₆        alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl,        C₁-C₆ haloalkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, C₃-C₁₀        trialkylsilyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₁-C₆        haloalkylamino, C₂-C₈ halodialkylamino, C₃-C₈ cycloalkylamino,        C₂-C₈ alkylcarbonylamino, C₂-C₈ haloalkylcarbonylamino, C₁-C₆        alkylsulfonylamino, C₁-C₆ haloalkylsulfonylamino, G^(A), G^(N)        and phenyl;    -   R² is H, cyano, hydroxy, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆        alkynyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆ haloalkynyl,        C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀ alkylcycloalkyl,        C₄-C₁₀ cycloalkylalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₂-C₈        alkoxyalkyl, C₄-C₁₀ cycloalkoxyalkyl or C₃-C₁₀        alkoxyalkoxyalkyl; or    -   R¹ and R² are taken together with the nitrogen to which they are        attached to form a 3- to 7-membered ring, containing ring        members, in addition to the nitrogen, selected from the group        consisting of C(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—,        —N═N—, C(═O), C(═S), C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) and        SiR^(5a)R^(5b);    -   each G^(A) is independently benzoyl, phenoxy or phenylsulfonyl        or a 5- or 6-membered heteroaromatic ring;    -   each G^(N) is independently a 3- to 7-membered nonaromatic        carbocyclic or heterocyclic ring, containing ring members        selected from the group consisting of C(R⁸)₂, O, S, NR³,        —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—, —N═N—, C(═O), C(═S), C(═NR⁴),        S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b);    -   each R³ is independently H, cyano, hydroxy, —C(═O)NH₂, C₁-C₆        alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₆        haloalkenyl, C₂-C₆ haloalkynyl, C₃-C₈ cycloalkyl, C₃-C₈        halocycloalkyl, C₄-C₁₀ alkylcycloalkyl, C₄-C₁₀ cycloalkylalkyl,        C₅-C₁₂ alkylcycloalkylalkyl, C₃-C₈ cycloalkenyl, C₂-C₈        alkoxyalkyl, C₄-C₁₀ cycloalkoxyalkyl, C₃-C₁₀ alkoxyalkoxyalkyl,        C₂-C₈ alkylthioalkyl, C₂-C₈ alkylsulfinylalkyl, C₂-C₈        alkylsulfonylalkyl, C₂-C₈ alkylaminoalkyl, C₄-C₁₀        dialkylaminoalkyl, C₃-C₈ haloalkylaminoalkyl, C₄-C₁₀        cycloalkylaminoalkyl, C₂-C₁₀ alkylcarbonyl, C₂-C₁₀        haloalkylcarbonyl, C₄-C₁₀ cycloalkylcarbonyl, C₂-C₁₀        alkoxycarbonyl, C₄-C₁₀ cycloalkoxycarbonyl, C₂-C₁₀        alkylaminocarbonyl, C₃-C₁₀ dialkylaminocarbonyl, C₄-C₁₀        cycloalkylaminocarbonyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₈        cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy,        C₂-C₈ alkoxyalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₃-C₈        cycloalkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl,        C₃-C₈ cycloalkylsulfonyl, C₃-C₅ trialkylsilyl or C₃-C₅        halotrialkylsilyl;    -   each R⁴ is independently H, cyano, amino, hydroxy, C₁-C₆ alkyl,        C₃-C₁₀ cycloalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ haloalkylcarbonyl,        C₁-C₆ alkoxy, phenyl or benzoyl;    -   each R^(5a) and R^(5b) is independently C₁-C₆ alkyl, C₂-C₆        alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl,        C₄-C₁₀ cycloalkylalkyl, C₄-C₁₀ alkylcycloalkyl, C₅-C₁₂        alkylcycloalkylalkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy or C₁-C₆        haloalkoxy;    -   G is benzoyl, phenoxy, phenylethynyl, phenylsulfonyl or        —(CR^(6a)R^(6b))_(n)G^(B);    -   G^(B) is a phenyl ring, naphthalenyl or a 5- to 6-membered        heteroaromatic ring, each ring optionally substituted with 1 to        5 substituents independently selected from R⁷;    -   each R^(6a) and R^(6b) is independently H, halogen, —C(═O)OH,        C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl,        C₃-C₈ halocycloalkyl, C₄-C₁₀ cycloalkylalkyl, C₄-C₈        alkylcycloalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₁-C₆ haloalkyl,        C₂-C₈ alkoxycarbonyl, C₁-C₆ alkoxy or C₁-C₆ haloalkoxy; or    -   R^(6a) and R^(6b) in geminal configuration are taken together        with the carbon atom to which they are attached to form a 3- to        7-membered ring, containing ring members, in addition to the        carbon atom, selected from the group consisting of C(R⁸)₂, O, S,        NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—, —N═N—, C(═O), C(═S), C(═NR⁴),        S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b);    -   R⁷ is halogen, cyano, hydroxy, amino, nitro, —CHO, —C(═O)OH,        —C(═O)NH₂, —SO₂NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl,        C₁-C₆ haloalkyl, C₂-C₈ alkylcarbonyl, C₂-C₈ haloalkylcarbonyl,        C₂-C₈ alkoxycarbonyl, C₄-C₁₀ cycloalkoxycarbonyl, C₅-C₁₂        cycloalkylalkoxycarbonyl, C₂-C₈ alkylaminocarbonyl, C₃-C₁₀        dialkylaminocarbonyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₈        alkylcarbonyloxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆        alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl,        C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylaminosulfonyl, C₂-C₈        dialkylaminosulfonyl, C₃-C₁₀ trialkylsilyl, C₁-C₆ alkylamino,        C₂-C₈ dialkylamino, C₂-C₈ alkylcarbonylamino, C₁-C₆        alkylsulfonylamino, phenyl, pyridinyl or thienyl;    -   each R⁸ is independently H, halogen, CN, C₁-C₃ alkyl or C₁-C₃        alkoxy;    -   X is N or CR^(9c);    -   Y is N or CR^(9d);    -   W is N or CR^(9e);    -   Z is N or CR^(9f);    -   each R^(9a), R^(9b), R^(9c), R^(9d), R^(9e) and R^(9f) is        independently H, halogen, nitro, CN, C₁-C₃ alkyl, C₁-C₃        haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy or C₁-C₃ haloalkoxy;    -   n is an integer selected from 0 through 6; and    -   p and q are independently 0, 1 or 2 in each instance of        S(═O)_(p)(═NR⁴)_(q), provided that the sum of p and q is 0, 1 or        2;

provided that:

-   -   (a) when R¹ is hydroxy, then R² is other than hydroxy; and    -   (b) at least one of X or Y is N.

More particularly, this invention pertains to a compound of Formula 1(including all geometric and stereoisomers), an N-oxide, or a saltthereof.

This invention also relates to a fungicidal composition comprising afungicidally effective amount of a compound of Formula 1 and at leastone additional component selected from the group consisting ofsurfactants, solid diluents or liquid diluents.

This invention also relates to a fungicidal composition comprising amixture of a compound of Formula 1 and at least one other fungicide.

This invention further relates to a method for controlling plantdiseases caused by fungal plant pathogens comprising applying to theplant or portion thereof, or to the plant seed or seedling, afungicidally effective amount of a compound of the invention (e.g., as acomposition described herein).

DETAILS OF THE INVENTION

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a composition,process, method, article, or apparatus that comprises a list of elementsis not necessarily limited to only those elements but may include otherelements not expressly listed or inherent to such composition, process,method, article, or apparatus. Further, unless expressly stated to thecontrary, “or” refers to an inclusive or and not to an exclusive or. Forexample, a condition A or B is satisfied by any one of the following: Ais true (or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and Both A and B are true (orpresent).

Also, use of “a” or “an” are employed to describe elements andcomponents of the invention. This is done merely for convenience and togive a general sense of the invention. This description should be readto include one or at least one and the singular also includes the pluralunless it is obvious that it is meant otherwise.

As referred to in the present disclosure and claims, “plant” includesmembers of Kingdom Plantae, particularly seed plants (Spermatopsida), atall life stages, including young plants (e.g., germinating seedsdeveloping into seedlings) and mature, reproductive stages (e.g., plantsproducing flowers and seeds). Portions of plants include geotropicmembers typically growing beneath the surface of the growing medium(e.g., soil), such as roots, tubers, bulbs and corms, and also membersgrowing above the growing medium, such as foliage (including stems andleaves), flowers, fruits and seeds.

As referred to herein, the term “seedling”, used either alone or in acombination of words means a young plant developing from the embryo of aseed.

In the above recitations, the term “alkyl”, used either alone or incompound words such as “alkylthio” or “haloalkyl” includesstraight-chain or branched alkyl, such as, methyl, ethyl, n-propyl,i-propyl, or the different butyl, pentyl or hexyl isomers. “Alkenyl”includes straight-chain or branched alkenes such as ethenyl, 1-propenyl,2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.“Alkenyl” also includes polyenes such as 1,2-propadienyl and2,4-hexadienyl. “Alkynyl” includes straight-chain or branched alkynessuch as ethynyl, 1-propynyl, 2-propynyl and the different butynyl,pentynyl and hexynyl isomers. “Alkynyl” can also include moietiescomprised of multiple triple bonds such as 2,5-hexadiynyl. “Alkoxy”includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy andthe different butoxy, pentoxy and hexyloxy isomers. “Alkoxyalkyl”denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” includeCH₃OCH₂, CH₃OCH₂CH₂, CH₃CH₂OCH₂, CH₃CH₂CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂.“Alkoxyalkoxy” denotes alkoxy substitution on alkoxy. “Alkenyloxy”includes straight-chain or branched alkenyloxy moieties. Examples of“alkenyloxy” include H₂C═CHCH₂O, (CH₃)₂C═CHCH₂O, CH₃CH═CHCH₂O,CH₃CH═C(CH₃)CH₂O and CH₂═CHCH₂CH₂O. “Alkynyloxy” includes straight-chainor branched alkynyloxy moieties. Examples of “alkynyloxy” includeHC≡CCH₂O, CH₃C≡CCH₂O and CH₃C≡CCH₂CH₂O. “Alkylthio” includes branched orstraight-chain alkylthio moieties such as methylthio, ethylthio, and thedifferent propylthio, butylthio, pentylthio and hexylthio isomers.“Alkylsulfinyl” includes both enantiomers of an alkylsulfinyl group.Examples of “alkylsulfinyl” include CH₃S(═O), CH₃CH₂S(═O),CH₃CH₂CH₂S(═O), (CH₃)₂CHS(═O) and the different butylsulfinyl,pentylsulfinyl and hexylsulfinyl isomers. Examples of “alkylsulfonyl”include CH₃S(O)₂, CH₃CH₂S(O)₂, CH₃CH₂CH₂S(O)₂, (CH₃)₂CHS(O)₂ and thedifferent butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.

“Alkylamino includes an NH radical substituted with straight-chain orbranched alkyl. Examples of “alkylamino” include CH₃CH₂NH, CH₃CH₂CH₂NH,and (CH₃)₂CHCH₂NH. Examples of “dialkylamino” include (CH₃)₂N,(CH₃CH₂CH₂)₂N and CH₃CH₂(CH₃)N. “Alkylaminoalkyl” denotes alkylaminosubstitution on alkyl. Examples of “alkylaminoalkyl” include CH₃NHCH₂,CH₃NHCH₂CH₂, CH₃CH₂NHCH₂, CH₃CH₂CH₂CH₂NHCH₂ and CH₃CH₂NHCH₂CH₂. Examplesof “dialkylaminoalkyl” include (CH₃)₂CH(CH₃)N, (CH₃CH₂CH₂)₂N andCH₃CH₂(CH₃)N. The term “alkylcarbonylamino” denotes alkyl bonded to aC(═O)NH moiety. Examples of “alkylcarbonylamino” include CH₃CH₂C(═O)NHand CH₃CH₂CH₂C(═O)NH.

The term “cycloalkyl” includes, for example, cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl. The term “cycloalkylalkyl” denotescycloalkyl substitution on an alkyl group. Examples of “cycloalkylalkyl”include cyclopropylmethyl, cyclopentylethyl, and other cycloalkylmoieties bonded to straight-chain or branched alkyl groups.“Alkylcycloalkyl” denotes alkyl substitution on a cycloalkyl moiety.Examples include 4-methylcyclohexyl and 3-ethylcyclopentyl.“Cycloalkenyl” includes groups such as cyclopentenyl and cyclohexenyl aswell as groups with more than one double bond such as 1,3- and1,4-cyclohexadienyl. The term “cycloalkoxy” denotes cycloalkyl attachedto and linked through an oxygen atom such as cyclopentyloxy andcyclohexyloxy. The term “cycloalkoxyalkyl” denotes cycloalkoxysubstitution on an alkyl moiety. Examples of “cycloalkoxyalkyl” includecyclopropyloxymethyl, cyclopentyloxyethyl, and other cycloalkoxymoieties bonded to straight-chain or branched alkyl groups.“Cycloalkylalkoxy” denotes cycloalkylalkyl attached to and linkedthrough an oxygen atom. Examples of “cycloalkylalkoxy” includecyclopropylmethoxy, cyclopentylethoxy, and other cycloalkyl moietiesbonded to straight-chain or branched alkoxy groups. The term“cycloalkylthio” denotes cycloalkyl attached to and linked through asulfur atom such as cyclopropylthio and cyclopentylthio;“cycloalkylsulfonyl” includes the corresponding sulfones.“Cycloalkylamino” denotes an NH radical substituted with cycloalkyl.Examples of “cycloalkylamino” include cyclopropylamino andcyclohexylamino. The term “cycloalkylaminoalkyl” denotes cycloalkylaminosubstitution on an alkyl group. Examples of “cycloalkylaminoalkyl”include cyclopropylaminomethyl, cyclopentylaminoethyl, and othercycloalkylamino moieties bonded to straight-chain or branched alkylgroups. “Cycloalkylcarbonyl” denotes cycloalkyl bonded to a C(═O) groupincluding, for example, cyclopropylcarbonyl and cyclopentylcarbonyl.

“Trialkylsilyl” includes three branched and/or straight-chain alkylradicals attached to and linked through a silicon atom such astrimethylsilyl, triethylsilyl and t-butyl-dimethylsilyl.

The term “alkylcarbonyl” denotes straight-chain or branched alkyl bondedto a C(═O) moiety. Examples of “alkylcarbonyl” include CH₃C(O),CH₃CH₂CH₂C(O) and (CH₃)₂CHC(O). Examples of “alkoxycarbonyl” includeCH₃OC(═O), CH₃CH₂OC(═O), CH₃CH₂CH₂C(═O), (CH₃)₂CHOC(═O) and thedifferent butoxy- or pentoxycarbonyl isomers. Examples of“alkylaminocarbonyl” include CH₃NHC(═O), CH₃CH₂NHC(═O),CH₃CH₂CH₂NHC(═O), (CH₃)₂CHNHC(═O) and the different butylamino- orpentylaminocarbonyl isomers. Examples of “dialkylaminocarbonyl” include(CH₃)₂NC(═O), (CH₃CH₂)₂NC(═O), CH₃CH₂(CH₃)NC(═O), (CH₃)₂CHN(CH₃)C(═O)and CH₃CH₂CH₂(CH₃)NC(═O)—.

The term “halogen”, either alone or in compound words such as“haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further,when used in compound words such as “haloalkyl”, said alkyl may bepartially or fully substituted with halogen atoms which may be the sameor different. Examples of “haloalkyl” include F₃C, ClCH₂, CF₃CH₂ andCF₃CCl₂. The terms “haloalkenyl”, “haloalkynyl”, “halocycloalkyl”,“haloalkoxy”, “haloalkylthio”, haloalkylamino and the like, are definedanalogously to the term “haloalkyl”. Examples of “haloalkenyl” include(Cl)₂C═CHCH₂ and CF₃CH₂CH═CHCH₂. Examples of “haloalkynyl” includeHC≡CCHCl, CF₃C≡C, CCl₃C≡C and FCH₂C≡CCH₂. Examples of “haloalkoxy”include CF₃O, CCl₃CH₂O, HCF₂CH₂CH₂O and CF₃CH₂O. Examples of“haloalkylthio” include CCl₃S, CF₃S, CCl₃CH₂S and ClCH₂CH₂CH₂S. Examplesof “haloalkylsulfinyl” include CF₃S(═O), CCl₃S(═O), CF₃CH₂S(═O) andCF₃CF₂S(═O). Examples of “haloalkylsulfonyl” include CF₃S(O)₂,CCl₃S(O)₂, CF₃CH₂S(O)₂ and CF₃CF₂S(O)₂. Examples of “haloalkylamino”include CF₃(CH₃)CHNH, (CF₃)₂CHNH and CH₂ClCH₂NH. Examples of“halodialkylamino” include (BrCH₂CH₂)₂N and BrCH₂CH₂(ClCH₂CH₂)N.

The total number of carbon atoms in a substituent group is indicated bythe “C_(i)-C_(j)” prefix where i and j are numbers from 1 to 12. Forexample, C₁-C₄ alkylsulfonyl designates methylsulfonyl throughbutylsulfonyl; C₂ alkoxyalkyl designates CH₃OCH₂; C₃ alkoxyalkyldesignates, for example, CH₃CH(OCH₃), CH₃OCH₂CH₂ or CH₃CH₂OCH₂; and C₄alkoxyalkyl designates the various isomers of an alkyl group substitutedwith an alkoxy group containing a total of four carbon atoms, examplesincluding CH₃CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂. C₂ alkylaminoalkyl designatesCH₃NHCH₂—; C₃ alkylaminoalkyl designates, for example, CH₃(CH₃NH)CH—,CH₃NHCH₂CH₂— or CH₃CH₂NHCH₂—; and C₄ alkylaminoalkyl designates thevarious isomers of an alkyl group substituted with an alkylamino groupcontaining a total of four carbon atoms, examples includingCH₃CH₂CH₂NHCH₂— and CH₃CH₂NHCH₂CH₂—.

When a compound is substituted with a substituent bearing a subscriptthat indicates the number of said substituents can vary, when the numberof said substituents is greater than 1, said substituents areindependently selected from the group of defined substituents. Further,when the subscript indicates a range, e.g. (R)_(i-j), then the number ofsubstituents may be selected from the integers between i and jinclusive. Also, one skilled in the art recognizes that the number ofavailable points of attachment is a limit of the number of substituentspossible and may be lower than the broad definition.

When a group contains a substituent which can be hydrogen, for exampleR¹, R², R³, R⁴, R^(6a), R^(6b), R⁸ or R⁹ then, when this substituent istaken as hydrogen, it is recognized that this is equivalent to saidgroup being unsubstituted at that position. The term “optionallysubstituted” without recitation of limitation in connection with thegroups listed for R¹ refers to groups that are unsubstituted or have atleast 1 non-hydrogen substituent. These groups may be substituted withas many optional substituents as can be accommodated by replacing ahydrogen atom with a non-hydrogen substituent on any available carbon ornitrogen atom. When the term “optionally substituted” is accompanied bya limit as for the groups listed for G^(B), the number of optionalsubstituents cannot exceed the limit even if further positions forsubstitution are available. Therefore, for example, the phrase“optionally substituted with 1 to 5 substituents” means than nosubstituent may be present, 1 substituent may be present, or up to 5substituents may be present if accommodated by the number of positionsavailable for substitution.

Naming of substituents in the present disclosure uses recognizedterminology providing conciseness in precisely conveying to thoseskilled in the art the chemical structure. For sake of conciseness,locant descriptors may be omitted; “pyrazol-1-yl” means“1H-pyrazol-1-yl” according to the Chemical Abstracts system ofnomenclature. The term “pyridyl” is synonymous with “pyridinyl”. Theorder of listing substituents may be different from the ChemicalAbstracts system if the difference does not affect the meaning.

Unless otherwise indicated, a “ring” as a component of Formula 1 (e.g.,substituent G^(N)) is carbocyclic or heterocyclic. The term “ringmember” refers to an atom or other moiety (e.g., C(═O), C(═S), S(O) orS(O)₂) forming the backbone of a ring or ring system.

“Aromatic” refers to a ring wherein each of the ring atoms isessentially in the same plane and has a p-orbital perpendicular to thering plane, and in which (4n+2) π electrons, where n is a positiveinteger, are associated with the ring to comply with Hückel's rule. Whena fully unsaturated carbocyclic ring satisfies Hückel's rule, then saidring is also called an “aromatic ring”. “Saturated carbocyclic” refersto a ring having a backbone consisting of carbon atoms linked to oneanother by single bonds; unless otherwise specified, the remainingcarbon valences are occupied by hydrogen atoms. The term “saturatedring” denotes a ring having a backbone consisting of atoms linked to oneanother by single bonds; unless otherwise specified, the remainingvalences are occupied by hydrogen atoms. In regards to degree ofsaturation, a “partially saturated ring” (alternatively described as a“partially unsaturated ring”) is intermediate between a saturated ringand a fully unsaturated ring (which may be aromatic). Therefore the term“partially saturated ring” (which may be carbocyclic or heterocyclicunless otherwise stated) denotes a ring comprising at least one ringmember bonded to an adjacent ring member through a double bond and alsocomprising at least one ring member bonded to an adjacent ring memberthrough a single bond that conceptually could be replaced by a doublebond to form a less saturated ring.

The terms “carbocyclic ring” or “carbocycle” denote a ring wherein theatoms forming the ring backbone are selected only from carbon. Unlessotherwise indicated, a carbocyclic ring can be a saturated, partiallysaturated, or fully unsaturated ring. When a fully unsaturatedcarbocyclic ring satisfies Hückel's rule, then said ring is also calledan “aromatic ring”. A carbocyclic ring that does not satisfy Hückel'srule is described as a “nonaromatic carbocyclic ring”.

The terms “heterocyclic ring” or “heterocycle” denote a ring in which atleast one atom forming the ring backbone is not carbon, e.g., nitrogen,oxygen or sulfur. Typically a heterocyclic ring contains no more than 4nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unlessotherwise indicated, a heterocyclic ring can be a saturated, partiallysaturated, or fully unsaturated ring. When a fully unsaturatedheterocyclic ring satisfies Hückel's rule, then said ring is also calleda “heteroaromatic ring” or “aromatic heterocyclic ring”. A heterocyclicring that does not satisfy Hückel's rule is described as a “nonaromaticheterocyclic ring”. The term “saturated heterocyclic ring” denotes aheterocyclic ring in which no ring member is bonded to an adjacent ringmember through a double bond. The term “partially saturated heterocyclicring” denotes a heterocyclic ring comprising at least one ring memberbonded to an adjacent ring member through a double bond and alsocomprising at least one ring member bonded to an adjacent ring memberthrough a single bond that conceptually could be replaced by a doublebond to form a less saturated heterocyclic ring. Unless otherwiseindicated, heterocyclic rings can be attached through any availablecarbon or nitrogen by replacement of a hydrogen on said carbon ornitrogen. In the above recitations, when a compound of Formula 1 iscomprised of one or more heterocyclic rings, substituents (if present)are attached to these rings through any available carbon or nitrogen byreplacement of a hydrogen on said carbon or nitrogen.

As noted above, G^(A) can be (among others) a 5- or 6-memberedheteroaromatic ring, optionally substituted with one or moresubstituents independently selected from a group of substituents asdefined in the Summary of the Invention. Examples of 5- or 6-memberedheteroaromatic rings optionally substituted with one or moresubstituents include the rings G-2 through G-61 illustrated in Exhibit 1wherein R^(v) is any substitutent as defined in the Summary of theInvention for G^(A)(i.e. as defined in R¹).

As noted above, G^(B) can be (among others) phenyl optionallysubstituted with up to 5 substituents selected from a group ofsubstituents as defined in the Summary of Invention. An example ofphenyl optionally substituted with up to five substituents is the ringillustrated as G-1 in Exhibit 1, wherein R^(v) is selected from a groupof substituents as defined in the Summary of the Invention forG^(B)(i.e., R⁷) and r is an integer from 0 to 5.

As noted above, G^(B) can be (among others) naphthalenyl, each ring ofwhich is stated to be optionally substituted with 1 to 5 substituents(independently selected from R⁷), which one skilled in the artrecognizes is limited by the number of available ring positions. As iswell known in the art, the naphthalenyl ring system consists of twophenyl rings fused together at adjacent carbon atoms. The ring ofnaphthalenyl attached to the remainder of Formula 1 has 3 positionsavailable for R⁷ substituents, and the other ring of naphthalenyl has 4positions available for R⁷ substituents.

As noted above, G^(B) can be (among others) a 5- or 6-memberedheteroaromatic ring, optionally substituted with up to 1 to 5substituents independently selected from a group of substituents asdefined in the Summary of the Invention. Examples of 5- or 6-memberedheteroaromatic rings optionally substituted with one or moresubstituents include the rings G-2 through G-61 illustrated in Exhibit 1wherein R^(v) is any substituent as defined in the Summary of theInvention for G^(B)(i.e., R⁷) and r is an integer from 0 to 5, limitedby the number of available positions on each G group. As G-29, G-30,G-36, G-37, G-38, G-39, G-40, G-41, G-42 and G-43 have only oneavailable position, for these G groups r is limited to the integers 0 or1, and r being 0 means that the G group is unsubstituted and a hydrogenis present at the position indicated by (R^(v))_(r).

Exhibit 1

As noted above, G^(N) can be (among others) a 3- to 7-memberednonaromatic heterocyclic ring. Examples of a 3-, 4-, 5- or 6-memberedsaturated or partially unsaturated heterocyclic ring include the ringsH-1 through H-48 as illustrated in Exhibit 2 wherein R^(v) is anysubstituent as defined in the Summary of the Invention for G^(N)(e.g. R³on nitrogen ring members, R⁴ on double-bonded nitrogen substituents,R^(5a) and R^(5b) on silicon ring members and R⁸ on carbon ring members)and r is typically an integer from 0 to 5, limited by the number ofavailable positions on each H-ring. The optional substituentscorresponding to (R^(v))_(r), can be attached to any available carbon ornitrogen by replacing a hydrogen atom. Note that when the attachmentpoint on the H-ring is illustrated as floating, the H-ring can beattached to the remainder of Formula 1 through any available carbon ornitrogen of the H-ring by replacement of a hydrogen atom.

Note that when G^(N) comprises a ring selected from H-33, H-34, H-35 andH-41 through H-45, G² is O, S or N. Note that when G² is N, the nitrogenatom can complete its valence by substitution with either H or thesubstituents corresponding to R³ as defined in the Summary of Invention.

Exhibit 2

As noted above, G^(N) can be (among others) a 3- to 7-memberednonaromatic carbocyclic ring. Examples of 3- to 7-membered nonaromaticcarbocyclic rings include the rings J-1 through J-9 as illustrated inExhibit 3 wherein R^(v) is any substituent on carbon as defined in theSummary of the Invention for G^(N)(i.e. R⁸).

Exhibit 3

One skilled in the art will appreciate that not all nitrogen-containingheterocycles can form N-oxides since the nitrogen requires an availablelone pair of electrons for oxidation to the oxide; one skilled in theart will recognize those nitrogen-containing heterocycles which can formN-oxides. One skilled in the art will also recognize that tertiaryamines can form N-oxides. Synthetic methods for the preparation ofN-oxides of heterocycles and tertiary amines are very well known by oneskilled in the art including the oxidation of heterocycles and tertiaryamines with peroxy acids such as peracetic and m-chloroperbenzoic acid(MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butylhydroperoxide, sodium perborate, and dioxiranes such asdimethydroxirane. These methods for the preparation of N-oxides havebeen extensively described and reviewed in the literature, see forexample: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik inComprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boultonand A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keenein Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R.Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advancesin Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J.Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G.Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A.R. Katritzky and A. J. Boulton, Eds., Academic Press.

Compounds of Formula 1 typically exist in more than one form, andFormula 1 thus include all crystalline and non-crystalline forms of thecompounds they represent. Non-crystalline forms include embodimentswhich are solids such as waxes and gums as well as embodiments which areliquids such as solutions and melts. Crystalline forms includeembodiments which represent essentially a single crystal type andembodiments which represent a mixture of polymorphs (i.e. differentcrystalline types). The term “polymorph” refers to a particularcrystalline form of a chemical compound that can crystallize indifferent crystalline forms, these forms having different arrangementsand/or conformations of the molecules in the crystal lattice. Althoughpolymorphs can have the same chemical composition, they can also differin composition due the presence or absence of co-crystallized water orother molecules, which can be weakly or strongly bound in the lattice.Polymorphs can differ in such chemical, physical and biologicalproperties as crystal shape, density, hardness, color, chemicalstability, melting point, hygroscopicity, suspensibility, dissolutionrate and biological availability. One skilled in the art will appreciatethat a polymorph of a compound of Formula 1 can exhibit beneficialeffects (e.g., suitability for preparation of useful formulations,improved biological performance) relative to another polymorph or amixture of polymorphs of the same compound of Formula 1. Preparation andisolation of a particular polymorph of a compound of Formula 1 can beachieved by methods known to those skilled in the art including, forexample, crystallization using selected solvents and temperatures.

Compounds of this invention can exist as one or more stereoisomers. Thevarious stereoisomers include enantiomers, diastereomers, atropisomersand geometric isomers. One skilled in the art will appreciate that onestereoisomer may be more active and/or may exhibit beneficial effectswhen enriched relative to the other stereoisomer(s) or when separatedfrom the other stereoisomer(s). Additionally, the skilled artisan knowshow to separate, enrich, and/or to selectively prepare saidstereoisomers. Accordingly, the present invention comprises compounds ofFormula 1, N-oxides or salts thereof. The compounds of the invention maybe present as a mixture of stereoisomers, individual stereoisomers, oras an optically active form. Compounds of Formula 1 can comprise chiralcenters. For example, the substituents R¹, R², R^(9a), R^(9b), R^(9c),R^(9d), R^(9e), R^(9f) and G may contain chiral centers. This inventioncomprises racemic mixtures as well as enriched and essentially purestereoconfigurations at these additional chiral centers.

When enantiomerically enriched, one enantiomer is present in greateramounts than the other, and the extent of enrichment can be defined byan expression of enantiomeric excess (“ee”), which is defined as(2x−1)·100%, where x is the mole fraction of the dominant enantiomer inthe mixture (e.g., an ee of 20% corresponds to a 60:40 ratio ofenantiomers).

Preferably the compositions of this invention have at least a 50%enantiomeric excess; more preferably at least a 75% enantiomeric excess;still more preferably at least a 90% enantiomeric excess; and the mostpreferably at least a 94% enantiomeric excess of the more active isomer.Of particular note are enantiomerically pure embodiments of the moreactive isomer.

Compounds of this invention can exist as one or more conformationalisomers due to the amide bonds in the compounds of Formula 1 as known byone skilled in the art. This invention comprises mixtures ofconformational isomers. In addition, this invention includes compoundsthat are enriched compared to the mixture of a conformer of Formula 1.

One skilled in the art recognizes that because in the environment andunder physiological conditions salts of chemical compounds are inequilibrium with their corresponding nonsalt forms, salts share thebiological utility of the nonsalt forms. Thus a wide variety of salts ofthe compounds of Formula 1 are useful for control of plant diseasescaused by fungal plant pathogens (i.e., are agriculturally suitable).The salts of the compounds of Formula 1 include acid-addition salts withinorganic or organic acids such as hydrobromic, hydrochloric, nitric,phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic,oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valericacids. When a compound of Formula 1 contains an acidic moiety such as acarboxylic acid or phenol, salts also include those formed with organicor inorganic bases such as pyridine, triethylamine or ammonia, oramides, hydrides, hydroxides or carbonates of sodium, potassium,lithium, calcium, magnesium or barium. Accordingly, the presentinvention comprises compounds selected from Formula 1, N-oxides andagriculturally suitable salts thereof.

Embodiments of the present invention as described in the Summary of theInvention include those described below. In the following Embodiments,Formula 1 includes N-oxides and salts thereof, and reference to “acompound of Formula 1” includes the definitions of substituentsspecified in the Summary of the Invention unless further defined in theEmbodiments.

Embodiment 1

A compound of Formula 1 wherein R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₂-C₈ alkylcarbonyl, C₂-C₈ alkoxycarbonyl, C₂-C₈alkylaminocarbonyl, C₃-C₁₀ dialkylaminocarbonyl, C₁-C₆ alkoxy, C₃-C₈cycloalkoxy, C₁-C₆ alkylthio, C₃-C₈ cycloalkylthio, C₁-C₆ alkylsulfinyl,C₁-C₆ alkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, G^(A) or G^(N), eachoptionally substituted with one or more substituents selected from thegroup consisting of halogen, cyano, hydroxy, amino, nitro, —CHO,—C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆haloalkyl, C₂-C₈ alkylcarbonyl, C₂-C₈ haloalkylcarbonyl, C₄-C₁₀cycloalkylcarbonyl, C₂-C₈ alkoxycarbonyl, C₄-C₁₀ cycloalkoxycarbonyl,C₂-C₈ alkylaminocarbonyl, C₃-C₁₀ dialkylaminocarbonyl, C₄-C₁₀cycloalkylamino carbonyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₈cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy, C₂-C₆alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆ alkynyloxy, C₃-C₆haloalkynyloxy, C₂-C₈ alkoxyalkoxy, C₂-C₈ alkylcarbonyloxy, C₂-C₈haloalkylcarbonyloxy, C₄-C₁₀ cycloalkylcarbonyloxy, C₁-C₆ alkylthio,C₁-C₆ haloalkylthio, C₃-C₈ cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₈cycloalkylsulfonyl, C₃-C₁₀ trialkylsilyl, C₁-C₆ alkylamino, C₂-C₈dialkylamino, C₁-C₆ haloalkylamino, C₂-C₈ halodialkylamino, C₃-C₈cycloalkylamino, C₂-C₈ alkylcarbonylamino, C₂-C₈ haloalkylcarbonylamino,C₁-C₆ alkylsulfonylamino, C₁-C₆ haloalkylsulfonylamino, G^(A), G^(N) andphenyl.

Embodiment 2

A compound of Embodiment 1 wherein R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl or G^(N), each optionally substituted with one or moresubstituents selected from the group consisting of halogen, cyano,hydroxy, amino, nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₆ alkylcarbonyl, C₂-C₈haloalkylcarbonyl, C₄-C₁₀ cycloalkylcarbonyl, C₂-C₈ alkoxycarbonyl,C₄-C₁₀ cycloalkoxycarbonyl, C₂-C₈ alkylaminocarbonyl, C₃-C₁₀dialkylaminocarbonyl, C₄-C₁₀ cycloalkylaminocarbonyl, C₁-C₆ alkoxy,C₁-C₆ haloalkoxy, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀cycloalkylalkoxy, C₂-C₆ alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆alkynyloxy, C₃-C₆ haloalkynyloxy, C₂-C₈ alkoxyalkoxy, C₂-C₈alkylcarbonyloxy, C₂-C₈ haloalkylcarbonyloxy, C₄-C₁₀cycloalkylcarbonyloxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₃-C₈cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, C₃-C₁₀trialkylsilyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₁-C₆haloalkylamino, C₂-C₈ halodialkylamino, C₃-C₈ cycloalkylamino, C₂-C₈alkylcarbonylamino, C₂-C₈ haloalkylcarbonylamino, C₁-C₆alkylsulfonylamino, C₁-C₆ haloalkylsulfonylamino, G^(A), G^(N) andphenyl.

Embodiment 3

A compound of Embodiment 2 wherein R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl or G^(N), each optionally substituted with one or moresubstituents selected from the group consisting of halogen, cyano,hydroxy, amino, nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy, C₂-C₆alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆ alkynyloxy, C₃-C₆haloalkynyloxy, C₂-C₈ alkoxyalkoxy, C₂-C₈ alkylcarbonyloxy, C₂-C₈haloalkylcarbonyloxy, C₄-C₁₀ cycloalkylcarbonyloxy, C₁-C₆ alkylthio,C₁-C₆ haloalkylthio, C₃-C₈ cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₈cycloalkylsulfonyl, C₃-C₁₀ trialkylsilyl and G^(N).

Embodiment 4

A compound of Embodiment 3 wherein R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl or G^(N), each optionally substituted with one or moresubstituents selected from the group consisting of halogen, cyano,hydroxy, amino, nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy, C₂-C₆alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆ alkynyloxy, C₃-C₆haloalkynyloxy, C₂-C₈ alkoxyalkoxy and G^(N).

Embodiment 5

A compound of Embodiment 4 wherein R¹ is 2-methoxy-1-methylethyl,2-ethoxy-1-methylethyl, 2-methoxy-1-ethylethyl, 2-ethoxy-1-ethylethyl,3-methoxy-1-methylpropyl, 3-ethoxy-1-methylpropyl,1-ethyl-3-methoxypropyl, 3-ethoxy-1-ethylpropyl ortetrahydro-2H-pyran-4-yl.

Embodiment 6

A compound of Embodiment 5 wherein R¹ is 2-methoxy-1-methylethyl ortetrahydro-2H-pyran-4-yl.

Embodiment 7

A compound of Embodiment 6 wherein R¹ is 2-methoxy-1-methylethyl.

Embodiment 8

A compound of Embodiment 6 wherein R¹ is tetrahydro-2H-pyran-4-yl.

Embodiment 9

A compound of Formula 1 or any one of Embodiments 1 through 8 wherein R²is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₃-C₈cycloalkyl, C₂-C₈ alkoxyalkyl, C₄-C₁₀ cycloalkoxyalkyl or C₃-C₁₀alkoxyalkoxyalkyl.

Embodiment 10

A compound of Embodiment 9 wherein R² is H or C₁-C₆ alkyl.

Embodiment 11

A compound of Embodiment 10 wherein R² is H.

Embodiment 12

A compound of Formula 1 wherein R¹ and R² are taken together with thenitrogen to which they are attached to form a 5- to 6-membered ringcontaining ring members, in addition to the nitrogen, selected from thegroup consisting of C(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—, —N═N—,C(═O), C(═S), C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b).

Embodiment 13

A compound of Embodiment 12 wherein R¹ and R² are taken together withthe nitrogen to which they are attached to form a 5-membered ring,containing ring members, in addition to the nitrogen, selected from thegroup consisting of C(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—, —N═N—,C(═O), C(═S), C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b);

Embodiment 14

A compound of Embodiment 13 wherein R¹ and R² are taken together to forma 4-methyl-2-oxo-3-oxazolidin-3-yl ring.

Embodiment 14A

A compound of Formula 1 wherein when R¹ and R² are taken together withthe nitrogen to which they are attached to form a ring, the ring is 5-or 6-membered.

Embodiment 14B

A compound of Embodiment 14A wherein when R¹ and R² are taken togetherwith the nitrogen to which they are attached to form a ring, the ring is5-membered.

Embodiment 15

A compound of Formula 1 or any one of Embodiments 1 through 14B whereineach R³ is independently H, cyano, hydroxy, —C(═O)NH₂, C₁-C₆ alkyl,C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆haloalkynyl, C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀alkylcycloalkyl, C₄-C₁₀ cycloalkylalkyl, C₅-C₁₂ alkylcycloalkylalkyl,C₃-C₈ cycloalkenyl, C₂-C₈ alkoxyalkyl, C₄-C₁₀ cycloalkoxyalkyl, C₃-C₁₀alkoxyalkoxyalkyl, C₂-C₈ alkylthioalkyl, C₂-C₈ alkylsulfinylalkyl, C₂-C₈alkylsulfonylalkyl, C₂-C₈ alkylaminoalkyl, C₄-C₁₀ dialkylaminoalkyl,C₃-C₈ haloalkylaminoalkyl or C₄-C₁₀ cycloalkylaminoalkyl.

Embodiment 16

A compound of Embodiment 15 wherein each R³ is independently H, cyano,—C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl,C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀ alkylcycloalkyl, C₄-C₁₀cycloalkylalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₂-C₈ alkoxyalkyl, C₄-C₁₀cycloalkoxyalkyl or C₃-C₁₀ alkoxyalkoxyalkyl.

Embodiment 17

A compound of Formula 1 or any one of Embodiments 1 through 16 wherein Gis —(CR^(6a)R^(6b))_(n)G^(B).

Embodiment 18

A compound of Embodiment 17 wherein G is G^(B).

Embodiment 19

A compound of Formula 1, or any one of Embodiments 1 through 18 whereinG^(B) is a phenyl ring, naphthalenyl or 5- to 6-membered heteroaromaticring, each ring optionally substituted with from 1 to 3 substituentsindependently selected from R⁷.

Embodiment 19A

A compound of Embodiment 19 wherein G^(B) is naphthalenyl or a phenyl orpyridinyl ring, each optionally substituted with up to 3 substituentsindependently selected from halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl andC₁-C₆ alkoxy.

Embodiment 20

A compound of Embodiment 19 wherein G^(B) is a 5-membered heteroaromaticring, optionally substituted with from 1 to 3 substituents independentlyselected from R⁷.

Embodiment 21

A compound of Embodiment 19 wherein G^(B) is a phenyl ring or 6-memberedheteroaromatic ring, each ring optionally substituted with up to 3substituents independently selected from R⁷.

Embodiment 22

A compound of Embodiment 19A or 21 wherein G^(B) is a phenyl orpyridinyl ring, each optionally substituted with up to 3 substituentsindependently selected from halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl andC₁-C₆ alkoxy.

Embodiment 23

A compound of Embodiment 22 wherein G^(B) is phenyl optionallysubstituted at the 3 and 5 positions with substituents selected fromhalogen and C₁-C₆ alkyl.

Embodiment 24

A compound of Embodiment 23 wherein G^(B) is phenyl optionallysubstituted at the 3 and 5 positions with halogen.

Embodiment 25

A compound of Embodiment 22 wherein G^(B) is phenyl optionallysubstituted at the 3 position with substituents selected from halogenand C₁-C₆ alkyl.

Embodiment 26

A compound of Embodiment 25 wherein G^(B) is phenyl optionallysubstituted at the 3 position with halogen.

Embodiment 27

A compound of Embodiment 22 wherein G^(B) is 3-pyridinyl or 4-pyridinyl,each optionally substituted with up to 3 substituents independentlyselected from halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl and C₁-C₆ alkoxy.

Embodiment 28

A compound of Embodiment 27 wherein G^(B) is 3-pyridinyl or 4-pyridinyl,each optionally substituted with up to 3 substituents independentlyselected from halogen and C₁-C₆ alkyl.

Embodiment 29

A compound of Formula 1 or any one of Embodiments 1 through 28 whereineach R^(6a) and R^(6b) is independently H.

Embodiment 30

A compound of Formula 1 or any one of Embodiments 1 through 29 whereineach R^(9a), R^(9b), R^(9c), R^(9d), R^(9e) and R^(9f) is independentlyH or halogen.

Embodiment 31

A compound of Embodiment 30 wherein each R^(9a), R^(9b), R^(9c), R^(9d),R^(9e) and R^(9f) is H.

Embodiment 32

A compound of Formula 1 or any one of Embodiments 1 through 31 whereineach X, W and Z is N and Y is CH; X is N and each Y, W and Z is CH; eachX, Y and W is N and Z is CH; each X and Z is N and each Y and W is CH;or each X and Z is CH and each Y and W is N.

Embodiment 33

A compound of Embodiment 32 wherein each X, W and Z is N and Y is CH.

Embodiment 34

A compound of Embodiment 32 wherein X is N and each Y, W and Z is CH.

Embodiment 35

A compound of Embodiment 32 wherein each X, Y and W is N and Z is CH.

Embodiment 36

A compound of Embodiment 32 wherein each X and Z is N and each Y and Wis CH.

Embodiment 37

A compound of Embodiment 32 wherein each X and Z is independently CH andeach Y and W is N.

Embodiments of this invention, including Embodiments 1-37 above as wellas any other embodiments described herein, can be combined in anymanner, and the descriptions of variables in the embodiments pertain notonly to the compounds of Formula 1 but also to the starting compoundsand intermediate compounds useful for preparing the compounds ofFormula 1. In addition, embodiments of this invention, includingEmbodiments 1-37 above as well as any other embodiments describedherein, and any combination thereof, pertain to the compositions andmethods of the present invention.

Combinations of Embodiments 1-37 are illustrated by:

Embodiment A1

A compound of Formula 1 wherein

-   -   R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl or G^(N), each        optionally substituted with one or more substituents selected        from the group consisting of halogen, cyano, hydroxy, amino,        -   nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆            alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆            haloalkoxy, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀            cycloalkylalkoxy, C₂-C₆ alkenyloxy, C₂-C₆ haloalkenyloxy,            C₂-C₆ alkynyloxy, C₃-C₆ haloalkynyloxy, C₂-C₈ alkoxyalkoxy            and G^(N);    -   R² is H or C₁-C₆ alkyl;    -   G is G^(B); and    -   each X, W and Z is N and Y is CH; X is N and each Y, W and Z is        CH; each X, Y and W is N and Z is CH; each X and Z is N and each        Y and W is CH; or each X and Z is CH and each Y and W is N.

Embodiment A2

A compound of Embodiment A1 wherein

-   -   R¹ is 2-methoxy-1-methylethyl, 2-ethoxy-1-methylethyl,        2-methoxy-1-ethylethyl, 2-ethoxy-1-ethylethyl,        3-methoxy-1-methylpropyl, 3-ethoxy-1-methylpropyl,        1-ethyl-3-methoxypropyl, 3-ethoxy-1-ethylpropyl or        tetrahydro-2H-pyran-4-yl;    -   R² is H; and    -   G^(B) is naphthalenyl or a phenyl or pyridinyl ring, each        optionally substituted with up to 3 substituents independently        selected from halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl and C₁-C₆        alkoxy.

Embodiment A3

A compound of Embodiment A2 wherein

-   -   R¹ is 2-methoxy-1-methylethyl or tetrahydro-2H-pyran-4-yl; and    -   G^(B) is phenyl optionally substituted at the 3 and 5 positions        with halogen.

Embodiment A4

A compound of Embodiment A3 wherein

-   -   G^(B) is phenyl optionally substituted at the 3 position with        halogen.

Specific embodiments include compounds of Formula 1 selected from thegroup consisting of:

-   N-(3,5-difluorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;-   4-[2-[(3-chlorophenyl)amino]-4-pyridinyl]-N-(2-methoxy-1-methylethyl)-2-pyrimidinamine;-   N-(3-fluorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;-   N-(3-fluorophenyl)-4-[2-[(2-methoxy-1-methylethyl)amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;    and-   4-[2-[(2-chloro-6-methylphenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine.

Of note are the above embodiments, including Embodiments 1 through 37and A1 through A4, wherein Formula 1 does not include N-oxides and saltsthereof.

This invention provides a fungicidal composition comprising a compoundof Formula 1 (including all geometric and stereoisomers, N-oxides, andsalts thereof), and at least one other fungicide. Of note as embodimentsof such compositions are compositions comprising a compoundcorresponding to any of the compound embodiments describe above.

This invention provides a fungicidal composition comprising afungicidally effective amount of a compound of Formula 1 (including allgeometric and stereoisomers, N-oxides, and salts thereof), and at leastone additional component selected from the group consisting ofsurfactants, solid diluents and liquid diluents. Of note as embodimentof such compositions are compositions comprising a compoundcorresponding to any of the compound embodiments describe above.

This invention provides a method for controlling plant diseases causedby fungal plant pathogens comprising applying to the plant or portionthereof, or to the plant seed or seedling, a fungicidally effectiveamount of a compound of Formula 1 (including all geometric andstereoisomers, N-oxides, and salts thereof). Of note as embodiment ofsuch methods are methods comprising applying a fungicidally effectiveamount of a compound corresponding to any of the compound embodimentsdescribe above. Of particular notes are embodiments where the compoundsare applied as compositions of this invention.

One or more of the following methods and variations as described inSchemes 1-23 can be used to prepare the compounds of Formula 1. Thedefinitions of R¹, R², R^(9a), R^(9b), R^(9c), R^(9d), R^(9e), R^(9f)and G in the compounds of Formulae 1-25a below are as defined above inthe Summary of the Invention unless otherwise noted. Formulae 1a-1e arevarious subsets of Formula 1, and all substituents for Formulae 1a-1eare as defined above for Formula 1.

As shown in Scheme 1, compounds of Formula 1a (Formula 1 wherein Y isCR^(9d) and X, W and Z are N) can be prepared by coupling of a compoundof Formula 3 with an amine of Formula 2 in the presence of acidscavenger. An excess of the amine of Formula 2 can also be used as anacid scavenger. Typical acid scavengers include amine bases such astriethylamine, N,N-diisopropylethylamine and pyridine. The reaction istypically conducted in a common organic solvent such as tetrahydrofuran,acetone, ethyl acetate, acetonitrile, N,N-dimethylformamide ordimethylsulfoxide in the presence of excess of the amine of Formula 2,usually in 2 to 10 equivalents relative to the compound of Formula 3.The reaction is typically conducted at a temperature of about 50° C. toabout 120° C. over a period of 0.5 to 20 h. When R¹ and R² are takentogether with the nitrogen to which they are attached to formsubstituted oxazolidin-2-ones, a palladium catalyst is needed toeffectively catalyze the reaction. Similar methods of displacingchloride from 2-chloropyridinyl-1,3,5-triazinyl derivatives with4-methyl-oxazolidin-2-one have been described in PCT Patent PublicationWO 2005/033095 A1.

As shown in Scheme 2, compounds of Formula 3 can be prepared by couplinga compound of Formula 5 with an amine of Formula 4 in a common organicsolvent such as tetrahydrofuran, acetone, ethyl acetate, acetonitrile,N,N-dimethylformamide or dimethylsulfoxide in the presence of excess ofthe amine of Formula 4, usually in 2 to 10 equivalents relative to thecompound of Formula 5. The reaction is typically run at room temperatureto about 60° C. over a period of about 1 to 20 h.

As shown in Scheme 3, compounds of Formula 5 can be prepared fromcompounds of Formula 6 by adding a solution prepared from mixingphosphorus(V) oxychloride and N,N-dimethylformamide to the compound ofFormula 6 to in acetonitrile at a temperature range from about −20° C.to 10° C. The reaction is typically run at 0° C. over a period of about12 to 20 h.

As shown in Scheme 4, the compound of Formula 6 can be prepared bytreatment of the compound of Formula 7 with cyanamide in a mixture ofwater and isopropanol in a ratio in the range of 1:1 to 4:1. Thereaction is typically run at room temperature over a period of about 10to 20 h.

As shown in Scheme 5, the compound of Formula 7 can be prepared bytreatment of the compound of Formula 8 with ammonia in methyl alcohol atroom temperature over a period of about 3 to 10 h.

As shown in Scheme 6, the compound of Formula 8 can be prepared bytreatment of commercially available compound 9 with hydrochloric acid inthe presence of methanol in a suitable organic solvent, such as toluene,benzene or methylene chloride. The reaction is typically run at atemperature from about 0° C. to about 20° C. over a period of about 8 to20 h.

As shown in Scheme 7, compounds of Formula 1b (Formula 1 wherein Z isCR^(9f) and W, X and Y are N) can be prepared by coupling a compound ofFormula 10 with an amine of Formula 4. The reaction is conducted in thepresence of 0.5 to 5 mol % of a palladium catalyst, such aspalladium(II) acetate or tris(dibenzylideneacetone)dipalladium(0), and 1to 10% of a ligand such as(±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene, and a base such ascesium carbonate. The reaction is typically run in a common organicsolvent such as tetrahydrofuran, toluene, or 1,4-dioxane at atemperature range from about 70° C. to about 120° C. over a period ofabout 0.5 to 20 h.

As shown in Scheme 8, compounds of Formula 10 can be prepared bycoupling a compound of Formula 5a with an amine of Formula 2. Thereaction is conducted in an organic solvent such as tetrahydrofuran,acetone, ethyl acetate, acetonitrile, N,N-dimethylformamide ordimethylsulfoxide in the presence of excess of the amine of Formula 2,usually in 2 to 10 equivalents relative to the compound of Formula 5a.The reaction is usually run at a temperature from about 0° C. to about30° C. over a period of about 0.5 to 20 h. Compounds of Formula 5a canbe prepared by methods analogous to methods for preparing compounds ofFormula 5 (e.g. Scheme 3).

As shown in Scheme 9, compounds of Formula 1c (Formula 1 wherein X is N,W is CR^(9e), Y is CR^(9d) and Z is CR^(9f)) can be prepared by couplinga compound of Formula 11 with an amine of Formula 4. The reaction isconducted with an excess of the amine of Formula 4, relative to compoundof Formula 11, in common organic solvents such as toluene and1,4-dioxane with heating at a temperature range of about 80° C. to about110° C. for 5 to 24 hours. The method typically involves palladiumcatalysts such as palladium(II) acetate ortris(dibenzylideneacetone)dipalladium(0) and ligands such as(±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene ((±)-BINAP),4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) or2-(di-t-butyl or dicyclohexylphosphino)biphenyl. An excess amount(usually 2 to 3 equivalents relative to the compound of Formula 11) ofbase, such as sodium t-butoxide, cesium carbonate or tribasic potassiumphosphate, is employed in these reactions. This Buchwald-Hartwig C—Nbond forming reactions are well known in the literature; general methodsfor forming C—N bonds can be found in Buchwald, S. L. et al, J. Org.Chem. 2000, 65, 1158-1174.

As shown in Scheme 10, compounds of Formula 11 can be prepared byheating compounds of Formula 12 with an excess amount of an amine ofFormula 2. The reaction is conducted neat or in common organic solventssuch as tetrahydrofuran, acetone, ethyl acetate, acetonitrile,N,N-dimethylformamide or dimethylsulfoxide, typically at temperaturesranging from about 50° C. to about 120° C. over a period of about 1 to20 h.

As shown in Scheme 11, compounds of Formula 12 can be prepared bytreatment of compounds of Formula 15 with a compound of Formula 13 inthe presence of palladium cross-coupling catalyst PdCl₂(dppf). Generalprocedures can be found from Negishi, E., et al. Handbook ofOrganopalladium Chemistry for Organic Synthesis Volumes 1 and 2, (2002).The intermediate compound of Formula 15 can be prepared from thecompound of Formula 14 (wherein X is Br or I) using isopropylmagnesiumchloride as reported by Queguiner, G. et al. Tetrahedron 2000, 56, 1349.Compounds of Formula 14 can be prepared by methods reported in Swahn, B.M. et al, Bioorg. Med. Chem. Lett. 2006, 16, 1397-1401.

As shown in Scheme 12, compounds of Formula 1c (Formula 1 wherein X isN, W is CR^(9e), Y is CR^(9d) and Z is CR^(9f)) can be prepared bytreatment of intermediates of Formula 16 with amines of Formula 2 underconditions as described in Scheme 1. When R¹ and R² are taken togetherwith the nitrogen to which they are attached to form substitutedoxazolidin-2-ones, a palladium catalyst is needed to effectivelycatalyze the reactions. Similar methods of displacing chloride from2-chloropyridinyl-1,3,5-triazinyl derivatives with4-methyl-oxazolidin-2-one have been described in PCT Patent PublicationWO 2005/033095 A1.

As shown in Scheme 13, compounds of Formula 16 can be prepared bycross-coupling of compounds of Formula 17 with a compound of Formula 13.This method is typically conducted in a solvent such as 1,4-dioxane,toluene or N-methyl-2-pyrrolidinone at temperatures from about 80° C. toabout 110° C. over a period from about 1 to 20 h in the presence ofpalladium catalysts such as bis(triphenylphosphine)palladium(II)dichloride or tetrakis(triphenylphosphine)palladium(0) and catalyticamounts of copper salts such as copper iodide.

As shown in Scheme 14, compounds of Formula 17 can be prepared byBuchwald-Hartwig C—N bond-forming reactions involving treatment ofcompounds of Formula 18 with amines of Formula 4 analogous to the methodof Scheme 9.

As shown in Scheme 15, compounds of Formula 18 can be prepared bytreatment of the pyridine of Formula 14a (Formula 14 wherein X is Br)with hexamethylditin in the presence of palladium catalyst such astetrakis(triphenylphosphine)palladium(0) orbis(triphenylphosphine)palladium(II) dichloride in organic solvents,such as 1,4-dioxane or tetrahydrofuran, at temperatures ranging fromabout 70° C. to about 120° C. over a period of 10 minutes to 5 h. Asimilar procedure was reported by Zhang, Y. et al. J. Med. Chem., 2004,47(10), 2453.

As shown in Scheme 16, compounds of Formula 1d (Formula 1 wherein X isCR^(9c), Z is CR^(9f) and W and Y are N) are prepared by heatingintermediates of Formula 19 with an excess amount of the amine ofFormula 4. Typically the reaction is conducted in the presence of acatalytic amount of p-toluenesulfonic acid monohydrate (PTSA) in1,4-dioxane at temperatures ranging from about 80° C. to about 120° C.over a period of 5 to 20 h. This method is disclosed in GB 2369359.

As shown in Scheme 17, compounds of Formula 19 can be prepared bycross-coupling a compound of Formula 20 with a compound of Formula 13aanalogous to the method of Scheme 13.

As shown in Scheme 18, compounds of Formula 20 can be prepared bytreatment of compounds of Formula 21 with hexamethylditin in thepresence of a palladium catalyst such asbis(triphenylphosphine)palladium(II) dichloride ortetrakis(triphenylphosphine)-palladium(0). Representative procedures canbe found in the literature, e.g., Undheim, K. et al. Tetrahedron 1989,45, 993-1006.

As shown in Scheme 19, compounds of Formula 21 can be prepared bytreatment of compounds of Formula 21a with an excess of amine of Formula2. Introduction of the amino group can be achieved by heating in a“closed vessel”, such as a microwave vial or pressure/bomb vessel, withorganic solvents such as 1,4-dioxane or N-methylpyrrolidinone in thepresence of a hindered base such as triethylamine orN,N-diisopropylethylamine at temperatures ranging from about 80° C. toabout 220° C. over a period of 0.3 to 20 h. Compounds of Formula 21a canbe prepared according to Boucher, E. et al, J. Org. Chem. 1995, 60,1408-1412.

As shown in Scheme 20, compounds of Formula 1e (Formula 1 wherein W isCR^(9e), Y is CR^(9d) and X and Z are N) can be prepared by coupling ofcompounds of Formula 22 with an excess amount of the amine of Formula 2.The reaction is conducted neat or in organic solvents such astetrahydrofuran, acetone, acetonitrile, N,N-dimethylformamide ordimethylsulfoxide typically at temperatures ranging from about 50° C. toabout 120° C. over a period of 1 to 20 h.

As shown in Scheme 21, compounds of Formula 22 can be prepared bytreatment of compounds of Formula 23 with an oxidizing reagent such asm-chloroperbenzoic acid (MCPBA) or Oxone® in organic solvents such aschloroform or dichloromethane at temperatures ranging from about 0° C.to about 20° C. over a period of 2 to 20 h.

As shown in Scheme 22, compounds of Formula 23 can be prepared bytreatment of compounds of Formula 25 with a compound of Formula 24analogous to the coupling method of Scheme 17. For a method ofpreparation of compounds of Formula 24 see Undheim, K. et al.Tetrahedron 1989, 45, 993-1006.

As shown in Scheme 23, compounds of Formula 25 can be prepared bycoupling a compound of Formula 25a with an amine of Formula 4. Thereaction is conducted in the presence of a hindered base such astriethylamine or N,N-diisopropylethylamine in solvents such asn-butanol, typically at temperatures ranging from about 50° C. to about120° C. over a period of 2 to 20 h.

Schemes 1 through 23 illustrate methods to prepare compounds of Formula1 having a wide variety of combinations of nitrogen and carbon radicalsfor X, Y, W and Z. Compounds of Formula 1 having other combinations ofnitrogen and carbon radicals for X, Y, W and Z can be prepared bygeneral methods known in the art of synthetic organic chemistry,including methods analogous to those described for Schemes 1 to 23.

It is recognized that some reagents and reaction conditions describedabove for preparing compounds of Formula 1 may not be compatible withcertain functionalities present in the intermediates. In theseinstances, the incorporation of protection/deprotection sequences orfunctional group interconversions into the synthesis will aid inobtaining the desired products. The use and choice of the protectinggroups will be apparent to one skilled in chemical synthesis (see, forexample, T. W. Greene and P. G. M. Wuts, Protective Groups in OrganicSynthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art willrecognize that, in some cases, after the introduction of a given reagentas it is depicted in any individual scheme, it may be necessary toperform additional routine synthetic steps not described in detail tocomplete the synthesis of compounds of Formula 1. One skilled in the artwill also recognize that it may be necessary to perform a combination ofthe steps illustrated in the above schemes in an order other than thatimplied by the particular sequence presented to prepare the compounds ofFormula 1.

One skilled in the art will also recognize that compounds of Formula 1and the intermediates described herein can be subjected to variouselectrophilic, nucleophilic, radical, organometallic, oxidation, andreduction reactions to add substituents or modify existing substituents.

Without further elaboration, it is believed that one skilled in the artusing the preceding description can utilize the present invention to itsfullest extent. The following Examples are, therefore, to be construedas merely illustrative, and not limiting of the disclosure in any waywhatsoever. Steps in the following Examples illustrate a procedure foreach step in an overall synthetic transformation, and the startingmaterial for each step may not have necessarily been prepared by aparticular preparative run whose procedure is described in otherExamples or Steps. Percentages are by weight except for chromatographicsolvent mixtures or where otherwise indicated. Parts and percentages forchromatographic solvent mixtures are by volume unless otherwiseindicated. Unless otherwise indicated, ¹H NMR spectra are reported inppm downfield from tetramethylsilane; “s” means singlet, “d” meansdoublet, “t” means triplet, “m” means multiplet, “q” means quartet, “dd”means doublet of doublets, “dt” means doublet of triplets, and “br s”means broad singlet. The abbreviation “m.p.” means melting point.

Example 1 Preparation ofN-(3-chlorophenyl)-4-[2-[(2-methoxy-1-methylethyl)amino]-4-pyrimidinyl]-1,3,5-triazine-2-amine(a compound of Formula 1) Step A: Preparation of2-chloro-N-cyano-4-pyrimidinecarboximidamide

To an ice-cooled solution of 2-chloro-4-pyrimidinecarbonitrile (23 g,0.16 mol) in toluene (500 mL) was added methanol (7.5 mL, 0.18 mol),followed by treatment with gaseous hydrogen chloride for 2 h. TheHCl-saturated solution was sealed and stirred overnight at roomtemperature, and then the white solid was collected by filtration andwashed with diethyl ether (200 mL) and ethyl acetate (200 mL). The solidwas then dissolved in methanol (400 mL) and treated with ammoniasolution (100 mL, 7 M in MeOH) at room temperature. After stirring 4 h,the solution was concentrated in vacuo and the residue washed with ethylacetate (200 mL). The resulting crude solid was dissolved in a mixtureof water (150 mL) and isopropanol (50 mL), and to this solution wasadded cyanamide (8.5 g, 0.2 mol), and sodium bicarbonate (9 g, 0.1 mol).The mixture was stirred at room temperature for 5 h, cooled to 0° C. andstirred for an additional 5 h. The resulting grey mixture was filtered,rinsed with water, and dried in vacuo for 24 h to give 13 g of the titlecompound as a white solid.

¹H NMR (DMSO-d₆) δ 9.32 (br s, 2H), 8.97 (d, 1H), 8.05 (d, 1H).

Step B: Preparation of2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine

To an ice-cooled solution of N,N-dimethylformamide (8.5 mL, 110 mmol) inmethylene chloride (100 mL) was added phosphorus oxychloride (8.0 mL, 87mmol) dropwise, and the mixture was stirred for 0.5 h. The resultingmixture was poured into a cold (0° C.) suspension of2-chloro-N-cyano-4-pyrimidinecarboximidamide (i.e., the product of StepA) (13 g, 73 mmol) in acetonitrile (200 mL). The resulting mixture wasstirred overnight in an ice bath. The mixture was passed through a shortsilica gel pad, eluted with 30% ethyl acetate in hexanes, andconcentrated under reduced pressure to give 7 g of the title compound asa white solid.

¹H NMR (CDCl₃) δ 9.30 (s, 1H), 8.97 (d, 1H), 8.43 (d, 1H).

Step C: Preparation ofN-(3-chlorophenyl)-4-[2-[(2-methoxy-1-methylethyl)amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine

To a solution of 2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine(i.e., the product of Step B) (25 mg, 0.11 mmol) in tetrahydrofuran (1.0mL) was added 3-chloroaniline (0.1 mL). The resulting mixture wasstirred at room temperature for 3 h to generate a yellow suspension. Tothis suspension was added 1-methoxy-2-propylamine (0.2 mL), and theresulting mixture was refluxed for 5 h. The solution was concentratedand purified using column chromatography on silica gel eluted with 70%ethyl acetate in hexanes to give 30 mg of the title compound as a yellowsolid.

¹H NMR (CDCl₃) δ 8.96 (s, 1H), 8.54 (d, 1H), 7.87 (br s, 2H), 7.55 (d,1H), 7.45 (br s, 1H), 7.28 (t, 1H), 7.12 (d, 1H), 5.83 (br s, 1H), 4.37(br s, 1H), 3.47 (m, 2H), 3.37 (s, 3H), 1.28 (d, 3H).

Example 2 Preparation ofN-(3-chlorophenyl)-4-[2-[(tetrahydro-2H-pyran-4-yl)amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine(a compound of Formula 1)

To a solution of 2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine(i.e., the product of Example 1, Step B) (25 mg, 0.11 mmol) intetrahydrofuran (1.0 mL) was added 3-chloroaniline (0.1 mL), and theresulting mixture was stirred at room temperature for 3 h to provide ayellow suspension. To this suspension added 4-aminotetrahydropyran (0.2mL), and the mixture was refluxed for 5 h. The solution was concentratedand purified using column chromatography on silica gel eluted with 70%ethyl acetate in hexanes to give 25 mg of the title compound as a yellowsolid.

¹H NMR (CDCl₃) δ 8.94 (s, 1H), 8.56 (d, 1H), 7.88 (br s, 1H), 7.75 (brs, 1H), 7.59 (d, 1H), 7.46 (d, 1H), 7.31 (t, 1H), 7.16 (d, 1H), 5.49 (brs, 1H), 4.15 (br s, 1H), 4.00 (m, 2H), 3.57 (m, 2H), 2.05 (m, 2H), 1.59(m, 2H).

Example 3 Preparation of5-[[4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazinyl]amino]-2-pyridinecarbonitrile(a compound of Formula 1)

To a solution of 2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine(i.e., the product of Example 1, Step B) (100 mg, 0.43 mmol) intetrahydrofuran (2.0 mL) was added 5-amino-2-pyridinecarbonitrile (86mg, 0.72 mmol), and the resulting mixture was stirred at 40° C. for 3 h.To this mixture was added (S)-1-methoxy-2-propylamine (0.2 mL), and theresulting mixture was refluxed for 2 h. The solution was concentratedand purified using column chromatography on silica gel eluted with agradient of 70% to 80% ethyl acetate in hexanes to give 84 mg of thetitle compound as a yellow solid.

¹H NMR (CDCl₃) δ 9.10 (s, 1H), 8.97 (s, 1H), 8.57 (d, 1H), 8.39 (br s,2H), 7.75 (d, 1H), 7.57 (d, 1H), 5.84 (br s, 1H), 4.37 (br s, 1H), 3.50(m, 2H), 3.40 (s, 3H), 1.31 (d, 3H).

Example 4 Preparation ofN-(3-fluoro-5-nitrophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine(a compound of Formula 1)

To a solution of 2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine(i.e., the product of Example 1, Step B) (68 mg, 0.30 mmol) intetrahydrofuran (2.0 mL) was added 3-fluoro-5-nitroaniline (72 mg, 0.46mmol), and the resulting mixture was stirred at 50° C. for 1 h to form ayellow suspension. To this suspension was added(S)-1-methoxy-2-propylamine (0.2 mL), and the resulting mixture wasrefluxed for 3 h. The solution was concentrated and purified usingcolumn chromatography on silica gel eluted with 70% ethyl acetate inhexanes to give 93 mg of the title compound as yellow solid.

¹H NMR (CDCl₃) δ 9.04 (s, 1H), 8.56 (d, 1H), 8.47 (br s, 2H), 7.99 (brs, 1H), 7.67 (m, 1H), 7.59 (d, 1H), 5.81 (br s, 1H), 4.38 (br s, 1H),3.50 (d, 2H), 3.40 (s, 3H), 1.30 (d, 3H).

Example 5 Preparation of4-[2-[(2-chloro-6-methylphenyl)amino]-4-pyrimidinyl]-N-(tetrahydro-2H-pyran-4yl)-1,3,5-triazin-2-amine(a compound of Formula 1) Step A: Preparation of the4-(2-chloro-4-pyrimidinyl)-N-(tetrahydro-2H-pyran-4-yl)-1,3,5-triazin-2-amine

To an ice-cooled solution of2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine (i.e., the product ofExample 1, Step B) (290 mg, 1.27 mmol) in tetrahydrofuran (20 mL) wasadded 4-aminotetrahydrofuran (284 mg, 2.8 mmol). The resulting mixturewas stirred at room temperature overnight and then concentrated andpurified using column chromatography on silica gel eluted with 60% ethylacetate in hexanes to give 300 mg of the title compound as a whitesolid.

¹H NMR (CDCl₃) δ 8.87 (d, 1H), 8.79 (s, 1H), 8.31 (d, 1H), 5.87 (d, 1H),4.20 (m, 1H), 4.02 (m, 2H), 3.56 (m, 2H), 2.06 (m, 2H), 1.63 (m, 2H).

Step B: Preparation of4-[2-[(2-chloro-6-methylphenyl)amino]-4-pyrimidinyl]-N-(tetrahydro-2H-pyran-4yl)-1,3,5-triazin-2-amine

To a solution of4-(2-chloro-4-pyrimidinyl)-N-(tetrahydro-2H-pyran-4-yl)-1,3,5-triazin-2-amine(i.e., the product of Step A) (125 mg, 0.42 mmol) in toluene (4.0 mL)under nitrogen was added 2-chloro-6-methylaniline (180 mg, 1.27 mmol),cesium carbonate (273 mg, 0.84 mmol),tris(dibenzylideneacetone)dipalladium(0) (20 mg, 0.022 mmol), and((±)-BINAP) (28 mg, 0.044 mmol), and the resulting mixture was stirredand heated at reflux for 6 h. After cooling to room temperature, themixture was concentrated and purified using column chromatography onsilica gel eluted with 40% acetone in hexanes to give 57 mg of the titlecompound as a yellow solid.

¹H NMR (CDCl₃) δ 8.79 (s, 1H), 8.53 (d, 1H), 7.70 (d, 1H), 7.31 (d, 1H),7.20 (m, 2H), 7.10 (s, 1H), 5.79 (d, 1H), 4.20 (m, 1H), 4.03 (m, 2H),3.55 (m, 2H), 2.29 (s, 3H), 2.06 (m, 2H), 1.62 (m, 2H).

Example 6 Preparation of4-[2-[(2-chloro-6-methylphenyl)amino]-4-pyridinyl]-N-(2-methoxy-1-methylethyl)-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine

Method A: To a cold solution (−40° C.) of 2-chloro-4-bromopyridine (9.5g, 49 mmol) in tetrahydrofuran (200 mL) was added isopropylmagnesiumchloride solution (25 mL, 2 M in THF) via syringe over 10 min. Theresulting light yellow solution was warmed to 0° C. over 2 h and stirredat 0° C. for 1 h under nitrogen to form a white suspension. To thissuspension was added[1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl₂(dppf)) (2.0 g, 2.0 mmol), followed by 2,4-dichloropyrimidine (7.4 g, 49mmol). After stirring at 0° C. for 10 min, the cold bath was removed.The mixture was allowed to stir overnight under nitrogen and thendiluted with ethyl acetate (300 mL). The resulting mixture was washedwith saturated aqueous ammonium chloride solution, dried over anhydrousmagnesium sulfate, and purified using column chromatography on silicagel eluted with 35% ethyl acetate in hexanes to give 6.3 g of the titlecompound as an off-white solid.

¹H NMR (CDCl₃) δ 8.80 (d, 1H), 8.60 (d, 1H), 8.01 (s, 1H), 7.86 (d, 1H),7.70 (d, 1H).

Method B: Under a nitrogen atmosphere, to a mixture of2,4-dichloropyrimidine (473 mg, 3.18 mmol), 2-chloro-4-pyridineboronicacid (500 mg, 3.18 mmol) and bis(triphenylphosphine)palladium(II)dichloride (67 mg, 0.095 mmol) in glyme (6.4 mL) was added 2 N aqueoussodium carbonate (3.35 mL) and methanol (1.67 mL), and the resultingmixture was stirred at 80° C. for 6 h. The solution was then cooled toroom temperature and diluted with de-ionized water and ethyl acetate.The layers were separated, and the aqueous layer was extracted twicewith ethyl acetate. The organic layers were combined and washed withsaturated sodium chloride solution, dried and concentrated to afford 760mg of crude residue, which was subjected to silica gel chromatographicpurification using 35% ethyl acetate in hexanes as eluant to give 435 mgof the title compound as an off-white solid.

Step B: Preparation of4-(2-chloro-4-pyridinyl)-N-(2-methoxy-1-methylethyl)-2-pyrimidinamine

A solution of 2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine (i.e., theproduct of Step A) (1.6 g, 7.0 mmol) in 1-methoxy-2-propylamine (5 mL)was stirred at reflux for 45 minutes. After cooling to room temperature,the mixture was purified using column chromatography on silica geleluted with 40% ethyl acetate in hexanes to give 1.4 g of the titlecompound as a white solid.

¹H NMR (CDCl₃) δ 8.51 (d, 1H), 8.43 (d, 1H), 7.94 (s, 1H), 7.78 (d, 1H),6.96 (d, 1H), 5.45 (d, 1H), 4.35 (m, 1H), 3.50 (d, 2H), 3.41 (s, 3H),1.33 (d, 3H).

Step C: Preparation of4-[2-[(2-chloro-6-methylphenyl)amino]-4-pyridinyl]-N-(2-methoxy-1-methylethyl)-2-pyrimidinamine

To a solution of4-(2-chloro-4-pyridinyl)-N-(2-methoxy-1-methylethyl)-2-pyrimidinamine(i.e., the product of Step B) (100 mg, 0.35 mmol) in toluene (10 mL) wasadded 2-chloro-6-methylaniline (102 mg, 0.72 mmol), cesium carbonate(350 mg, 1.07 mmol), palladium(II) acetate (4 mg, 0.017 mmol) and((±)-BINAP) (22 mg, 0.035 mmol), and the resulting mixture was stirredat reflux for 30 h. After cooling to room temperature, the mixture wasconcentrated, and purified using column chromatography on silica geleluted with 40% ethyl acetate in hexanes to give 30 mg of the titlecompound as a solid.

¹H NMR (CDCl₃) δ 8.33 (d, 1H), 8.29 (d, 1H), 7.36 (d, 1H), 7.25 (m, 2H),7.14 (t, 1H), 6.84 (m, 2H), 6.60 (s, 1H), 5.43 (d, 1H), 4.24 (m, 1H),3.45 (d, 2H), 3.36 (s, 3H), 2.30 (s, 3H), 1.24 (d, 2H).

Example 7 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of1-(methylthio)-2-propanone oxime

To a solution of 1-(methylthio)-2-propanone (10.2 mL, 99.7 mmol) in 120mL water was added hydroxylamine hydrochloride (8.9 g, 122 mmol)followed by the addition of sodium bicarbonate (8.4 g, 99.9 mmol)portion-wise over 15 min. The resulting suspension was stirred at roomtemperature for 72 h and then extracted with diethyl ether (200 mL). Theorganic layer was washed twice with brine (150 mL), dried over MgSO₄,filtered and concentrated to give 11.0 g of the title compound as aclear oil.

¹H NMR (CDCl₃) δ 3.17 (s, 2H), 2.03 (s, 3H), 2.00 (s, 3H).

Step B: Preparation of 1-(methylthio)-2-propanamine

To a stirred solution of 1-(methylthio)-2-propanone oxime (i.e., theproduct of Step A) (8.3 g, 64.2 mmol) in diethyl ether (150 mL) wasadded lithium aluminum hydride (2.4 g, 64.2 mmol) portion-wise over 15minutes, while maintaining the temperature of the reaction mixture below30° C. The stirred mixture was allowed to warm to room temperature for24 h. To this mixture was added sequentially over 0.5 h, water (2.4 g),15% aqueous sodium hydroxide (2.4 g) and water (7.2 g). The resultingmixture was then stirred at room temperature for 1.5 h. The resultingsuspension was filtered through a pad of Celite® filter aid, and thefiltrate was concentrated under reduced pressure to give 6.9 g of thetitle compound as an oil.

¹H NMR (CDCl₃) δ 3.04-3.13 (m, 1H), 2.56-2.63 (m, 1H), 2.34-2.42 (m,1H), 2.11 (s, 3H), 1.17 (d, 3H).

Step C: Preparation4-(2-chloro-4-pyridinyl)-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine

To a solution of 2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine (i.e., theproduct of Example 6, Step A) (350 mg, 1.5 mmol) in toluene (4.0 mL) wasadded 1-(methylthio)-2-propanamine (i.e., the product of Step B) (1 mL,9.5 mmol) in one portion; this mixture was heated at 60° C. for 18 h.The mixture was allowed to cool and silica gel (300 mg) was added. Theexcess solvent was removed under reduced pressure, and the resultingsolid was chromatographed on silica gel eluted with a solvent gradientof 5% to 60% ethyl acetate in hexanes to give 400 mg (88%) of the titlecompound as a tan solid, m.p. 103-106° C.

¹H NMR (CDCl₃) δ 8.50 (d, 1H), 8.43 (d, 1H), 7.94 (s, 1H) 7.77 (d, 1H),6.98 (d, 1H), 5.32-5.43 (m, 1H), 4.31-4.45 (m, 1H), 2.78-2.88 (m, 1H),2.65-2.75 (m, 1H), 2.18 (s, 3H), 1.39 (d, 3H).

Step D: Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine

To a solution of4-(2-chloro-4-pyridinyl)-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine(i.e., the product of Step C) (150 mg, 0.5 mmol) in toluene (6.0 mL) wasadded 3-fluoroaniline (108 μL, 1.1 mmol), palladium(II) acetate (24 mg,0.12 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene((±)-BINAP) (40 mg, 0.06 mmol) and cesium carbonate (700 mg, 2.2 mmol);the resulting mixture was stirred at 110° C. for 13 h. The mixture wasallowed to cool and silica gel (300 mg) was added. The excess solventwas removed under reduced pressure, and the resulting solid waschromatographed on silica gel eluted with 5% to 60% ethyl acetate inhexanes to give 60 mg of the title compound as a yellow solid, m.p.104-107° C.

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 8.35 (d, 1H), 7.52 (s, 1H), 7.25-7.38 (m,3H), 7.07-7.12 (m, 1H), 6.96 (d, 1H), 6.71-6.79 (m, 2H), 5.32 (d, 1H),4.33-4.44 (m, 1H), 2.79-2.86 (m, 1H), 2.68-2.75 (m, 1H), 2.15 (s, 3H),1.38 (d, 3H).

Example 8 Preparation of4-[2-[(3-chlorophenyl)amino]-4-pyridinyl]-N-[1-methyl-2-(methylthio)ethyl]-2-pyrimidinamine(a compound of Formula 1)

The title compound was prepared in the same fashion as described inExample 7, Step D using 3-chloroaniline in place of 3-fluoroaniline.

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 8.34 (d, 1H), 7.48-7.61 (m, 2H),7.27-7.32 (m, 2H), 7.24-7.26 (m, 1H), 6.99-7.04 (m, 1H), 6.94 (d, 1H),6.77 (s, 1H), 5.36 (d, 1H), 4.32-4.43 (m, 1H), 2.77-2.85 (m, 1H),2.67-2.75 (m, 1H), 2.13 (s, 3H), 1.37 (d, 3H).

Example 9 Preparation ofN-cyclopentyl-4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of4-(2-chloro-4-pyridinyl)-N-cyclopentyl-2-pyrimidinamine

Cyclopentylamine (3 mL) was combined with2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine (i.e., the product ofExample 6, Step A) (300 mg, 1.3 mmol) and stirred at 55° C. for 2 hours.The resulting suspension was filtered, and the collected solid was ovendried at 50° C. in vacuo to give 340 mg of the title compound as a brownsolid.

¹H NMR (CDCl₃) δ 8.51 (d, 1H), 8.43 (d, 1H), 7.94 (s, 1H), 7.79 (d, 1H),6.95 (d, 1H), 5.27 (d, 1H), 4.32-4.42 (m, 1H), 2.07-2.19 (m, 2H),1.64-1.83 (m, 4H), 1.49-1.59 (m, 2H).

Step B: Preparation ofN-cyclopentyl-4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-2-pyrimidinamine

The title compound was prepared in the same fashion as described inExample 7, Step D using4-(2-chloro-4-pyridinyl)-N-cyclopentyl-2-pyrimidinamine (i.e., theproduct of Step A) and 3-fluoroaniline.

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 8.34 (d, 1H), 7.56 (br s, 1H), 7.35-7.37(m, 1H), 7.29-7.34 (m, 2H), 7.09 (d, 1H), 6.93 (d, 1H), 6.71-6.79 (m,2H), 5.22 (d, 1H), 4.30-4.39 (m, 1H), 2.04-2.16 (m, 2H), 1.64-1.79 (m,4H), 1.50-1.57 (m, 2H).

Example 10 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine

The title compound was prepared in the same fashion as described inExample 9, Step A using 4-aminotetrahydrofuran in place ofcyclopentylamine to obtain 300 mg of the title compound as a tan solid,m.p. 156-158° C.

¹H NMR (CDCl₃) δ 8.51 (d, 1H), 8.43 (d, 1H), 7.90-7.93 (m, 1H), 7.77 (d,1H), 6.98 (d, 1H), 5.22 (d, 1H), 4.09-4.17 (m, 1H), 3.99-4.06 (m, 2H),3.54-3.63 (m, 2H), 2.09 (d, 2H), 1.59-1.67 (m, 2H).

Step B: Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine

To a solution of4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(i.e., the product of Step A) (500 mg, 1.7 mmol) in toluene (15 mL) wasadded 3-fluoroaniline (400 uL, 4.1 mmol), palladium(II) acetate (50 mg,0.20 mmol), (±)-BINAP (100 mg, 0.16 mmol) and cesium carbonate (1.9 g,5.8 mmol), and the resulting mixture was stirred at reflux for 4.5 h.The cooled mixture was partitioned between ethyl acetate and water, andthe organic layer was washed with brine, dried over MgSO₄ and filtered.The solvent was removed under reduced pressure to give a residue thatwas chromatographed on silica gel eluted with 15% to 85% ethyl acetatein hexanes to afford 330 mg of title compound as a solid, m.p. 190-192°C.

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 8.36 (d, 1H), 7.53 (br s, 1H), 7.33-7.38(m, 1H), 7.28-7.32 (m, 2H), 7.08 (d, 1H), 6.96 (d, 1H), 6.73-6.82 (m,1H), 6.71 (s, 1H), 5.17 (d, 1H), 4.09-4.20 (m, 1H), 3.97-4.07 (m, 2H),3.51-3.61 (m, 2H), 2.06-2.12 (m, 2H), 1.59-1.67 (m, 2H).

Example 11 Preparation of4-[2-[(3-chlorophenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(a compound of Formula 1)

The title compound was prepared in the same fashion as described inExample 10, Step B using4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(i.e., the product of Example 10, Step A) and 3-chloroaniline to give 75mg of the title compound as a tan solid.

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 8.35 (d, 1H), 7.53 (s, 1H), 7.50 (br s,1H), 7.30 (d, 1H), 7.02-7.06 (m, 1H), 6.96 (d, 1H), 6.67 (br s, 1H),5.17 (d, 1H), 4.10-4.17 (m, 1H), 3.98-4.05 (m, 2H), 3.52-3.60 (m, 2H),2.08 (d, 2H), 1.59-1.65 (m, 2H).

Example 12 Preparation of4-[2-[(2-chlorophenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(a compound of Formula 1)

The title compound was prepared in the same fashion as described inExample 10, Step B using4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(i.e., the product of Example 10, Step A) and 2-chloroaniline to give124 mg of the title compound as a tan solid, m.p. 153-156° C.

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 8.37 (d, 1H), 8.11 (d, 1H), 7.50 (s, 1H),7.42 (dd, 1H), 7.28-7.33 (m, 1H), 7.25-7.28 (m, 1H), 6.97-7.04 (m, 1H),6.95-6.97 (m, 2H), 5.20 (d, 1H), 4.06-4.18 (m, 1H), 4.01 (dt, 2H), 3.55(t, 2H), 2.08 (d, 2H), 1.53-1.64 (m, 2H).

Example 13 Preparation of4-[2-[(4-chloro-2-methylphenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(a compound of Formula 1)

The title compound was prepared in the same fashion as described inExample 10, Step B using4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(i.e., the product of Example 10, Step A) and 2-methyl-4-chloroanilineto give 40 mg of the title compound as a solid, m.p. 196-198° C.

¹H NMR (CDCl₃) δ 8.36 (d, 1H), 8.28 (d, 2H), 7.43 (d, 1H), 7.16-7.26 (m,3H), 6.90 (d, 1H), 6.49 (br s, 1H), 5.25 (d, 1H), 3.97-4.08 (m, 3H),3.51 (t, 2H), 2.27 (s, 3H), 2.01 (br s, 2H), 1.51-1.63 (m, 2H).

Example 14 Preparation of4-[2-[(2-chloro-4-methylphenyl)amino]-4-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(a compound of Formula 1)

The title compound was prepared in the same as described in Example 10,Step B using4-(2-chloro-4-pyridinyl)-N-(tetrahydro-2H-pyran-4-yl)-2-pyrimidinamine(i.e., the product of Example 10, Step A) and 2-chloro-4-methylanilineto give 137 mg of the title compound as a tan solid, m.p. 184-186° C.

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 8.35 (d, 1H), 7.89 (d, 1H), 7.44 (s, 1H),7.25-7.30 (m, 2H), 7.09 (dd, 1H), 6.96 (d, 1H), 6.85 (s, 1H), 5.16 (d,1H), 3.98-4.05 (m, 2H), 3.55 (dt, 2H), 2.33 (s, 3H), 2.03-2.11 (m, 2H),1.54-1.64 (m, 2H).

Example 15 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[(tetrahydro-3-furanyl)methyl]-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of(tetrahydro-3-furanyl)methyl 4-methylbenzenesulfonate

To a solution of tetrahydro-3-furanmethanol (6.2 g, 60.8 mmol) in 60 mLtetrahydrofuran was added p-toluenesulfonyl chloride (11.6 g, 60.9 mmol)in one portion, followed by the drop-wise addition of triethylamine (9.2mL, 66.4 mol) over 10 min. The resulting mixture was stirred at refluxfor 16 h and then treated with triethylamine (1.6 mL, 11.5 mmol).Heating was continued for an additional 18 h. The cooled mixture wasdiluted with diethyl ether, washed with water and brine, and dried overMgSO₄. The mixture was then filtered and concentrated under reducedpressure. The resulting residue was placed on a column of silica gel (30g) and eluted with 5% to 80% ethyl acetate in hexanes to give 11.0 g(72%) of the title compound as an orange oil.

¹H NMR (CDCl₃) δ 7.79 (m, 2H), 7.36 (m, 2H), 3.88-4.04 (m, 2H),3.64-3.84 (m, 3H), 3.50 (dd, 1H), 2.53-2.67 (m, 1H), 2.46 (s, 3H),1.96-2.05 (m, 1H), 1.50-1.64 (m, 1H).

Step B: Preparation of2-[(tetrahydro-3-furanyl)methyl]-1H-isoindole-1,3(2H)-dione

To a solution of (tetrahydro-3-furanyl)methyl 4-methylbenzenesulfonate(i.e., the product of Step A) (11.0 g, 42.9 mmol) inN,N-dimethylformamide (160 mL) was added potassium phthalimide (7.9 g,42.7 mmol) in one portion, and the resulting mixture was stirred at 80°C. for 6 h. Additional potassium phthalimide (5 g, 27 mmol) was added,and stirring was continued at 100° C. for 18 h. The cooled reactionmixture was partitioned between water and ethyl acetate and the aqueouslayer was separated and extracted with ethyl acetate (5×75 mL). Thecombined extracts were dried over MgSO₄ and filtered, and the solventwas removed under reduced pressure to give a residue which waschromatographed on silica gel (40 g) eluted with 5% to 100% ethylacetate in hexanes to give 4.5 g of the title compound as a white solid,m.p. 114-118° C.

¹H NMR (CDCl₃) δ 7.87 (dd, 2H), 7.74 (dd, 2H), 3.94 (dt, 1H), 3.67-3.87(m, 4H), 3.62 (dd, 1H), 2.70-2.79 (m, 1H), 1.97-2.07 (m, 1H), 1.74 (dt,1H).

Step C: Preparation of tetrahydro-3-furanmethanamine

To a solution of2-[(tetrahydro-3-furanyl)methyl]-1H-isoindole-1,3(2H)-dione (i.e., theproduct of Step B) (4.5 g, 19.5 mmol) in ethanol (150 mL) was addedhydrazine monohydrate (4.75 mL, 97.5 mmol) drop-wise over 5 minutes. Theresulting mixture was stirred at reflux for 90 minutes during which timea suspension formed, followed by dissolution to form a solution. Thecooled solution was diluted with 200 mL diethyl ether, and the resultingsuspension was filtered. Excess solvent was removed under reducedpressure to give a residue, which was filtered through a pad of Celite®.The solvent was removed under reduced pressure to give 2.5 g of thetitle compound as a clear oil.

¹H NMR (CDCl₃) δ 3.82-3.91 (m, 1H), 3.72-3.78 (m, 1H), 3.51 (dd, 1H),2.72 (d, 2H), 2.23-2.35 (m, 2H), 1.99-2.10 (m, 1H), 1.53-1.63 (m, 1H).

Step D: Preparation of4-(2-chloro-4-pyridinyl)-N-[(tetrahydro-3-furanyl)methyl]-2-pyrimidinamine

The title compound was prepared from2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine (i.e., the product ofExample 6, Step A) and tetrahydro-3-furanmethanamine (i.e., the productof Step C) in the same fashion as described in Example 9, Step A.

¹H NMR (CDCl₃) δ 8.51 (d, 1H), 8.43 (d, 1H), 7.93 (s, 1H), 7.78 (d, 1H),6.99 (d, 1H), 5.46 (br s, 1H), 3.86-3.98 (m, 2H), 3.79 (dt, 1H), 3.66(dd, 1H), 3.54 (t, 2H), 2.58-2.72 (m, 1H), 2.03-2.18 (m, 1H), 1.73 (dt,1H).

Step E: Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[(tetrahydro-3-furanyl)methyl]-2-pyrimidinamine

The title compound was prepared in the same fashion as described inExample 10, Step B using4-(2-chloro-4-pyridinyl)-N-[(tetrahydro-3-furanyl)methyl]-2-pyrimidinamine(i.e., the product of Step D) and 3-fluoroaniline to give 115 mg of thetitle compound as a tan solid, m.p. 154-156° C.

¹H NMR (CDCl₃) δ 8.40 (d, 1H), 8.36 (d, 1H), 7.53 (br s, 1H), 7.33-7.39(m, 1H), 7.27-7.33 (m, 2H), 7.10 (dd, 1H), 6.97 (d, 1H), 6.71-6.79 (m,2H), 5.35 (t, 1H), 3.85-3.97 (m, 2H), 3.74-3.82 (m, 1H), 3.65 (dd, 1H),3.53 (t, 2H), 2.59-2.70 (m, 1H), 2.06-2.15 (m, 1H), 1.67-1.77 (m, 1H).

Example 16 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[(tetrahydro-2-furanyl)methyl]-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of4-(2-chloro-4-pyridinyl)-N-[(tetrahydro-2-furanyl)methyl]-2-pyrimidinamine

The title compound was prepared from2-chloro-4-(2-chloro-4-pyridinyl)pyrimidine (i.e., the product ofExample 6, Step A) and tetrahydrofurfurylamine in the same fashion asdescribed in Example 9, Step A, m.p. 74-75° C.

¹H NMR (CDCl₃) δ 8.51 (d, 1H), 8.43 (d, 1H), 7.94 (s, 1H), 7.79 (dd,1H), 6.97 (d, 1H), 5.61 (br s, 1H), 4.08-4.19 (m, 1H), 3.94 (dt, 1H),3.79-3.85 (m, 1H), 3.71-3.79 (m, 1H), 3.55 (br s, 1H), 1.90-2.11 (m,3H), 1.62-1.73 (m, 1H).

Step B:4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-[(tetrahydro-2-furanyl)methyl]-2-pyrimidinamine

The title compound was prepared in the same fashion as described inExample 10, Step B using4-(2-chloro-4-pyridinyl)-N-[(tetrahydro-2-furanyl)methyl]-2-pyrimidinamine(i.e., the product Step A) and 3-fluoroaniline to give 90 mg of thetitle compound as a brown solid.

¹H NMR (CDCl₃) δ 8.38 (d, 1H), 8.31 (d, 1H), 7.24-7.37 (m, 3H), 7.21 (brs, 1H), 7.09 (dd, 1H), 6.92 (d, 1H), 6.75 (dt, 1H), 5.67 (br s, 1H),4.08-4.18 (m, 1H), 3.87-3.98 (m, 1H), 3.76-3.85 (m, 1H), 3.68-3.76 (m,1H), 3.52 (br s, 1H), 1.88-2.06 (m, 3H), 1.60-1.71 (m, 1H).

Example 17 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(2-methoxypropyl)-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of2-chloro-4-trimethylstannylpyridine

To a solution of 2-chloro-4-bromopyridine (16 g, 83 mmol) in 1,4-dioxane(250 mL) was added hexamethyldistannane (30 g, 91 mmol) andbis(triphenylphosphine)palladium(II) dichloride (2.6 g, 3 mmol). Theresulting mixture was stirred at reflux for 30 min under nitrogen. Aftercooling to room temperature, the solution was concentrated and theresidue was purified via column chromatography on silica gel eluted with10% ethyl acetate in hexanes to give 30 g of title compound as colorlessoil.

¹H NMR (CDCl₃) δ 8.26 (d, 1H), 7.40 (s, 1H), 7.28 (d, 1H), 0.35 (s, 9H).

Step B: Preparation ofN-(3-fluorophenyl)-4-trimethylstannyl)-2-pyridinamine

To a solution of 2-chloro-4-trimethylstannylpyridine (i.e., the productof Step A) (10 g, 36 mmol) in toluene (200 mL) was added 3-fluoroaniline(6.0 g, 54 mmol), cesium carbonate (23 g, 70 mmol), palladium(II)acetate (406 mg, 1.8 mmol) and (±)-BINAP (2.2 g, 3.4 mmol). Theresulting mixture was stirred at 100° C. for 5 h. After cooling to roomtemperature, the mixture was diluted with ethyl acetate (200 mL), washedwith water and brine, and dried over anhydrous magnesium sulfate. Themixture was filtered, concentrated under reduced pressure and purifiedusing column chromatography on silica gel eluted with 10% ethyl acetatein hexanes to afford 4.5 g of title compound as colorless oil.

¹H NMR (CDCl₃) δ 8.16 (m, 1H), 7.33 (d, 1H), 7.24 (m, 1H), 7.06 (d, 1H),6.96 (s, 1H), 6.88 (d, 1H), 6.68 (t, 1H), 6.60 (br s, 1H), 0.31 (s, 9H).

Step C: Preparation of4-(2-chloro-4-pyrimidinyl)-N-(3-fluorophenyl)-2-pyridinamine

To a solution of N-(3-fluorophenyl)-4-trimethylstannyl)-2-pyridinamine(i.e., the product of Step B) (4.0 g, 11 mmol) in 1,4-dioxane (100 mL)under nitrogen was added 2,4-dichloropyrimidine (2.26 g, 15 mmol),copper iodide (216 mg, 1.1 mmol) andbis(triphenylphosphine)palladium(II) dichloride (400 mg, 0.57 mmol). Theresulting mixture was stirred at reflux for 4 h. After cooling to roomtemperature, the solution was concentrated under reduced pressure. Theresulting residue was purified using column chromatography on silica geleluted with 25% ethyl acetate in hexanes to afford 2.3 g of titlecompound as a yellow solid.

¹H NMR (CDCl₃) δ 8.75 (d, 1H), 8.41 (d, 1H), 7.65 (d, 1H), 7.53 (s, 1H),7.43 (m, 1H), 7.32 (m, 1H), 7.29 (m, 1H), 7.11 (m, 1H), 6.77 (m, 2H).

Step D: Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(2-methoxypropyl)-2-pyrimidinamine

To a solution of4-(2-chloro-4-pyrimidinyl)-N-(3-fluorophenyl)-2-pyridinamine (i.e., theproduct of Step C) (55 mg, 0.18 mmol) in toluene (3.0 mL) was added2-methoxy-1-aminopropane hydrochloride (125 mg, 1.0 mmol) and potassiumcarbonate (200 mg, 1.5 mmol). The mixture was stirred at 100° C. for 2 hand then allowed to cool to room temperature. The mixture waspartitioned with water and ethyl acetate and the water layer wasdecanted. The organic layer was washed with brine and passed through aCelite® containing drying tube. The solvent was evaporated, and theresulting residue was chromatographed using 5% to 60% ethyl acetate inhexanes as eluant to give an oil which solidified upon standing. Thissolid was suspended in hexanes, filtered and washed with hexanes to give25 mg of the title compound as a yellow solid, m.p. 103-105° C.

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 8.34 (d, 1H), 7.52 (br s, 1H), 7.33-7.39(m, 1H), 7.26-7.32 (m, 2H), 7.09 (d, 1H), 6.94 (d, 1H), 6.74 (dt, 1H),6.68 (br s, 1H), 5.52-5.62 (m, 1H), 3.73 (m, 1H), 3.58 (dt, 1H),3.38-3.41 (m, 3H), 3.32-3.38 (m, 1H), 1.22 (d, 3H).

Example 18 Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(3-methoxy-1-methylpropyl)-2-pyrimidinamine(a compound of Formula 1) Step A: Preparation of 4-methoxy-2-butanoneoxime

To a 1 N solution of hydrogen chloride (2 mL) was added1,3,3-trimethyoxybutane (15 g, 101 mmol) drop-wise over 5 minutes, andthe resulting mixture was stirred at 50° C. for 30 min. Sodiumbicarbonate (5 g) was added to the cooled mixture, followed by diethylether, and MgSO₄. Filtration followed by the evaporation of the solventyielded 8.5 g of a yellow oil. This oil was dissolved in methanol (100mL) and cooled to 15° C. Hydroxylamine hydrochloride (8 g, 115 mmol) andaqueous sodium hydroxide (50%, 15 mL, 192 mmol) were added alternatelyat a rate to maintaining the internal temperature below 30° C. Themixture was stirred at room temperature for 72 h and then partitionedbetween diethyl ether and water. The organic layer was dried over MgSO₄and filtered. The solvent was removed under reduced pressure to give 2.0g of the title compound as a yellow oil.

¹H NMR (CDCl₃) δ 8.32 (br s, 1H), 3.54-3.61 (m, 2H), 3.35 (s, 3H), 2.47(t, 2H), 1.92 (s, 3H).

Step B: Preparation of 3-methoxy-1-methylpropylamine

3-Methoxy-1-methyl-propylamine was prepared from 4-methoxy-2-butanoneoxime (i.e., the product of Step B) in the same fashion as described inExample 7, Step B to give the title compound as an oil.

¹H NMR (CDCl₃) δ 3.40-3.53 (m, 2H), 3.33 (s, 3H), 3.01-3.11 (m, 1H),1.51-1.69 (m, 2H), 1.06-1.12 (m, 3H).

Step C: Preparation of4-[2-[(3-fluorophenyl)amino]-4-pyridinyl]-N-(3-methoxy-1-methylpropyl)-2-pyrimidinamine

The title compound was prepared from 3-methoxy-1-methylpropylamine(i.e., the product of Step B) and4-(2-chloro-4-pyrimidinyl)-N-(3-fluorophenyl)-2-pyridinamine (i.e., theproduct of Example 17, Step C) in the same fashion as described inExample 17, Step D to give the title compound as a yellow solid, m.p.104-106° C.

¹H NMR (CDCl₃) δ 8.39 (d, 1H), 8.35 (d, 1H), 7.56 (br s, 1H), 7.37 (dt,1H), 7.25-7.34 (m, 2H), 7.10 (dd, 1H), 6.92 (d, 1H), 6.70-6.78 (m, 2H),5.41 (d, 1H), 4.32 (m, 1H), 3.46-3.62 (m, 2H), 3.34 (s, 3H), 1.88 (dt,2H), 1.31 (d, 3H).

Example 19 Preparation ofN²-(3-chlorophenyl)-N⁶′-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1) Step A:Preparation of 6-iodo-N-(2-methoxy-1-methylethyl)-4-pyrimidinamine

4,6-Diiodo-pyrimidine is a known compound and was prepared according toTaft, W. E. et al. J. Med. Pharm. Chem., 1962, 5, 1335.

A microwave vial was charged with 4,6-diiodopyrimidine (2.0 g, 6.02mmol), 2-aminomethoxypropane (763 μL, 7.23 mmol), triethylamine (2.1 mL,15.06 mmol) and N-methylpyrrolidinone (16 mL). The resulting solutionwas microwaved for 20 min at 200° C., then poured into water andextracted with diethyl ether (3×30 mL). The organic layers were combinedand washed three times with de-ionized water, then dried andconcentrated. The residue was subjected to silica gel chromatographicpurification using a gradient of hexanes to 40% ethyl acetate in hexanesas eluant to afford 2.0 g of the title compound as an oil.

¹H NMR (CDCl₃) δ 8.2 (s, 1H), 6.8 (s, 1H), 5.1 (br s, 1H), 4.1 (br s,1H), 3.4 (m, 2H), 3.3 (s, 3H), 1.2 (d, 3H).

Step B: Preparation ofN-(2-methoxy-1-methylethyl)-6-(trimethylstannyl)-4-pyrimidinamine

To a solution of 6-iodo-N-(2-methoxy-1-methylethyl)-4-pyrimidinamine(i.e., the product of Step A) (2.0 g, 6.82 mmol) andhexamethyldistannane (2.34 g, 7.16 mmol) in 1,4-dioxane (70 mL) under anitrogen atmosphere was added bis(triphenyl phosphine)palladium(II)dichloride (0.14 g, 0.205 mmol). The resulting mixture was stirred atreflux for 3 h. After cooling to room temperature the solution wasdiluted with water and extracted with ethyl acetate. The organic layerswere combined and washed three times with water, dried and concentratedto give 2.2 g of the title compound.

¹H NMR (CDCl₃) δ 8.6 (s, 1H), 6.5 (s, 1H), 4.8 (br s, 1H), 4.1 (br s,1H), 3.4 (m, 2H), 3.3 (s, 3H), 1.2 (d, 3H), 0.3 (s, 9H).

Step C: Preparation of 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine

To a solution ofN-(2-methoxy-1-methylethyl)-6-(trimethylstannyl)-4-pyrimidinamine (i.e.,the product of Step B) (0.5 g, 1.51 mmol), 2,4-dichloropyrimidine (0.22g, 1.51 mmol) and copper iodide (12 mg, 0.061 mmol) inN-methylpyrrolidinone (12 mL) under a nitrogen atmosphere was addedbis(triphenylphosphine)palladium(II) dichloride (53 mg, 0.076 mmol). Theresulting mixture was stirred at reflux for 2 h. After cooling to roomtemperature, the solution was diluted with water and extracted withdiethyl ether 3 times. The organic layers were combined and washed threetimes with water, then dried and concentrated. The residue was purifiedon silica gel using a gradient of 100% hexanes to 40% ethyl acetate inhexanes to afford 270 mg of title compound as a solid.

¹H NMR (CDCl₃) δ 8.8 (d, 1H), 8.6 (s, 1H), 8.2 (d, 1H), 7.46 (s, 1H),5.4 (br s, 1H), 4.3 (br s, 1H), 3.4 (m, 2H), 3.3 (s, 3H), 1.3 (d, 3H).

Step D: Preparation of N²-(3-chlorophenyl)-N⁶′-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine

To a solution of 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Step C) (100 mg, 0.357mmol) and 3-chloroaniline (57 mg, 0.45 mmol) in 1,4-dioxane (3.5 mL)under a nitrogen atmosphere was added p-toluenesulfonic acid monohydrate(57 mg, 0.30 mmol). The resulting mixture was stirred at 100° C. for 18h. The solution was concentrated under reduced pressure to give a yellowsolid residue. The residue was then purified on silica gel eluted with40% ethyl acetate in hexanes, followed by acetone to give 113 mg oftitle compound as a solid.

¹H NMR (CDCl₃) δ 9.8 (s, 1H), 8.4 (s, 1H), 8.3 (d, 1H), 7.9 (d, 2H), 7.8(s, 1H), 7.5 (d, 1H), 7.1-7.2 (m, 2H), 6.9 (d, 1H), 4.4 (m, 1H), 3.4 (m,2H), 3.3 (s, 3H), 1.2 (d, 3H).

Example 20 Preparation ofN²-(3-fluorophenyl)-N⁶′-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1)

The title compound was prepared in the same manner as described inExample 19, Step D using 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Example 19, Step C)and 3-fluoroaniline to give the title compound as a solid.

¹H NMR (DMSO-d₆) δ 10.1 (br s, NH), 8.9 (d, 1H), 8.7 (d, 2H), 7.6-7.8(m, 2H), 7.4 (m, 2H), 7.3 (m, 1H), 7.1 (d, 1H), 6.8 (m, 1H), 6.6 (m,1H), 4.4 (m, 1H), 3.4 (m, 2H), 3.3 (s, 3H), 1.2 (d, 3H).

Example 21 Preparation ofN⁶′-(2-methoxy-1-methylethyl)-N²-(3-nitrophenyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1)

The title compound was prepared in the same manner as described inExample 19, Step D using 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Example 19, Step C)and 3-nitroaniline to give the title compound as a solid.

¹H NMR (acetone-d₆) δ 10.8 (br s, 1H), 9.4 (br s, 1H), 8.9 (s, 1H), 8.7(d, 2H), 8.1 (d, 1H), 7.9 (s, 1H), 7.8 (d, 2H), 7.5-7.6 (m, 2H), 7.2 (d,2H), 4.6 (m, 1H), 3.4 (m, 2H), 3.3 (s, 3H), 1.2 (d, 3H).

Example 22 Preparation of N⁶′-(2-methoxy-1-methylethyl)-N²-phenyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1)

The title compound was prepared in the same manner as described inExample 19, Step D using 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Example 19, Step C)and aniline to give the title compound as a solid.

¹H NMR (CDCl₃) δ 9.6 (s, 1H), 8.4 (s, 1H), 8.3 (br s, 1H), 7.9 (d, 2H),7.6 (br s, 2H), 7.2 (m, 3H), 6.9 (br s, 1H), 4.4 (br s, 1H), 3.4 (m,2H), 3.3 (s, 3H), 1.2 (d, 3H).

Example 23 Preparation ofN²-(2-chloro-6-methylphenyl)-N⁶′-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1)

The title compound was prepared in the same manner as described inExample 19, Step D using 2′-chloro-N-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Example 19, Step C)and 2-chloro-6-methylaniline to give the title compound as a solid.

¹H NMR (CDCl₃) δ 8.6 (br s, 1H), 8.3 (br s, 1H), 7.9 (br s, 2H), 7.6 (brs, 1H), 7.4 (br s, 1H), 7.1-7.2 (m, 2H), 4.4 (br s, 1H), 3.4 (m, 2H),3.3 (s, 3H), 2.35 (m, 3H), 1.2 (d, 3H).

Example 24 Preparation ofN⁶′-(3-fluorophenyl)-N²-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine (a compound of Formula 1) Step A:Preparation of N-(3-fluorophenyl)-6-iodo-4-pyrimidinamine

A mixture of 4,6-diiodopyrimidine (1.0 g, 3.01 mmol), 3-fluoroaniline(290 μL, 3.01 mmol), N,N-diisopropylethylamine (782 μL, 4.52 mmol) andn-butanol (3 mL) under nitrogen was stirred at 120° C. for 4 h. Aftercooling to room temperature, the solution was poured into water andextracted with ethyl acetate. The organic layer was washed once with 1 Nhydrochloric acid, followed by brine, dried and concentrated to yield0.68 g of title compound.

¹H NMR (DMSO-d₆) δ 9.8 (s, 1H), 8.3 (s, 1H), 7.7 (d, 1H), 7.3-7.4 (m,2H), 6.8 (m, 1H).

Step B: Preparation of 2′-methylthio-N-(3-fluorophenyl)[4,4′-bipyrimidine]-6-amine

2-Methylthio-4-tri-n-butylstannylpyrimidine was prepared according toUndheim, K. et al. Tetrahedron 1989, 45, 993-1006.

To a solution of 2-methylthio-4-(tri-n-butylstannyl)pyrimidine (0.29 g,1.0 mmol) and N-(3-fluorophenyl)-6-iodo-4-pyrimidinamine (i.e., theproduct of Step A) (0.67 g, 2.12 mmol) in N-methylpyrrolidinone (10 mL)under nitrogen was added copper iodide (16 mg, 0.085 mmol) andbis(triphenylphosphine)palladium(II) dichloride (149 mg, 0.21 mmol). Theresulting mixture was stirred at 100° C. for 2.5 h. After cooling toroom temperature, the solution was diluted with ethyl acetate and washedwith water. The aqueous layer was extracted two times with ethylacetate, and the combined organic layers were washed with water andbrine, dried and concentrated to give 259 mg of the title compound as alight brown solid.

¹H NMR (DMSO-d₆) δ 10.2 (br s, 1H), 8.8 (m, 2H), 8.0 (d, 1H), 7.8 (m,2H), 7.3-7.4 (m, 2H), 6.8 (m, 1H), 2.64 (s, 3H).

Step C: Preparation of 2′-methylsulfonyl-N-(3-fluorophenyl)[4,4′-bipyrimidine]-6-amine

To a solution of 2′-methylthio-N-(3-fluorophenyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Step B) (259 mg, 0.826mmol) in dichloromethane (6 mL) and chloroform (12 mL) was addedm-chloroperoxybenzoic acid (370 mg, 77%). The resulting mixture wasstirred at room temperature for 3 h. The mixture was then diluted withdichloromethane and washed with saturated sodium bisulfite solution,followed by saturated sodium bicarbonate solution, dried andconcentrated to provide 390 mg of the title compound a yellow solid.

¹H NMR (DMSO-d₆) δ 10.4 (br s, 1H), 9.3 (d, 1H), 8.9 (s, 1H), 8.6 (d,1H), 7.96 (s, 1H), 7.9 (d, 1H), 7.3-7.4 (m, 2H), 6.8 (m, 1H), 3.51 (s,3H).

Step D: Preparation of N⁶′-(3-fluorophenyl)-N²-(2-methoxy-1-methylethyl)[4,4′-bipyrimidine]-2,6′-diamine

A mixture of 2′-methylsulfonyl-N-(3-fluorophenyl)[4,4′-bipyrimidine]-6-amine (i.e., the product of Step C) (290 mg, 0.841mmol) and 2-aminomethoxypropane (5 mL) was stirred at 100° C. for 2 hunder a nitrogen atmosphere. The solution was concentrated and theresidue was dissolved in dichloromethane and washed with water andbrine. The organic layer was dried, and concentrated, and the solidresidue was washed with diethyl ether to give 122 mg of title compoundwas obtained as a solid.

¹H NMR (DMSO-d₆) δ 8.8 (s, 1H), 8.4 (d, 1H), 7.8 (s, 1H), 7.5 (d, 1H),7.3-7.4 (m, 2H), 7.2 (m, 1H), 6.8 (t, 1H), 5.4 (d, 1H), 4.3 (m, 1H),3.48 (m, 2H), 3.38 (s, 3H), 1.3 (d, 3H).

By the procedures described herein, together with methods known in theart, the following compounds of Tables 1 to 7 can be prepared. Thefollowing abbreviations are used in the Tables which follow: t meanstertiary, s means secondary, n means normal, means iso, c means cyclo,Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl,c-Pr means cyclopropyl, Bu means butyl, Hex means hexyl, Ph meansphenyl, MeO means methoxy, CN means cyano, SO₂ means S(O)₂, and NO₂means nitro. (R) or (S) denotes the absolute chirality of the asymmetriccarbon center. The radicals CH₂-2-tetrahydrofuranyl,CH₂-2-tetrahydropyranyl, CH₂-2-dioxolanyl, CH₂-2-thienyl,CH₂-2-pyridinyl and CH₂-3-pyridinyl are bonded to the remainder of themolecule through the CH₂ moiety.

The invention includes but is not limited to the following exemplaryspecies.

TABLE 1

R¹ R^(7a) R^(7b) R^(7c) Me H 3-F H Et H 3-F H i-Pr H 3-F H n-Pr H 3-F Hi-Bu H 3-F H n-Bu H 3-F H s-Bu H 3-F H t-butyl H 3-F H n-Hex H 3-F Hcyclopropyl H 3-F H cyclopentyl H 3-F H cyclohexyl H 3-F H2-cyclohexenyl H 3-F H 3-cyclohexenyl H 3-F H CH₂-c-Pr H 3-F H4-tetrahydropyranyl H 3-F H 3-tetrahydropyranyl H 3-F H(R)-3-tetrahydropyranyl H 3-F H (S)-3-tetrahydropyranyl H 3-F H3-tetrahydrofuranyl H 3-F H (R)-3-tetrahydrofuranyl H 3-F H(S)-3-tetrahydrofuranyl H 3-F H Ph H 3-F H 2-Cl-phenyl H 3-F H3-Cl-phenyl H 3-F H 4-Cl-phenyl H 3-F H 2-pyridinyl H 3-F H2-pyrimidinyl H 3-F H Me 3-Cl 5-F H Et 3-Cl 5-F H i-Pr 3-Cl 5-F H n-Pr3-Cl 5-F H i-Bu 3-Cl 5-F H n-Bu 3-Cl 5-F H s-Bu 3-Cl 5-F H t-butyl 3-Cl5-F H n-Hex 3-Cl 5-F H cyclopropyl 3-Cl 5-F H cyclopentyl 3-Cl 5-F Hcyclohexyl 3-Cl 5-F H 2-cyclohexenyl 3-Cl 5-F H 3-cyclohexenyl 3-Cl 5-FH CH₂-c-Pr 3-Cl 5-F H 4-tetrahydropyranyl 3-Cl 5-F H 3-tetrahydropyranyl3-Cl 5-F H (R)-3-tetrahydropyranyl 3-Cl 5-F H (S)-3-tetrahydropyranyl3-Cl 5-F H 3-tetrahydrofuranyl 3-Cl 5-F H (R)-3-tetrahydrofuranyl 3-Cl5-F H (S)-3-tetrahydrofuranyl 3-Cl 5-F H Ph 3-Cl 5-F H 2-Cl-phenyl 3-Cl5-F H 3-Cl-phenyl 3-Cl 5-F H 4-Cl-phenyl 3-Cl 5-F H 2-pyridinyl 3-Cl 5-FH 2-pyrimidinyl 3-Cl 5-F H 2-pyrazinyl H 3-F H 2-thiazolyl H 3-F H2-oxazolyl H 3-F H 2-chloro-2-propenyl H 3-F H 3,3-dichloro-2-propenyl H3-F H CH₂-2-tetrahydrofuranyl H 3-F H CH₂-2-tetrahydropyranyl H 3-F HCH₂CH₂OH H 3-F H CH₂OMe H 3-F H CH₂CH₂OMe H 3-F H CH₂CH₂CH₂OMe H 3-F HCH₂CH(Me)OMe H 3-F H CH(Me)OMe H 3-F H CH(Me)OEt H 3-F H CH(Me)CH₂OMe H3-F H C(Me)₂CH₂OMe H 3-F H CH(Me)CH₂CH₂OMe H 3-F H (R)—CH(Me)CH₂OMe H3-F H (S)—CH(Me)CH₂OMe H 3-F H CH(Me)CH₂OH H 3-F H CH(Me)CH₂OC(═O)Me H3-F H CH(Me)CH(OMe)₂ H 3-F H CH₂-2-dioxolanyl H 3-F H CH₂CH₂OCF₃ H 3-F HCH₂CH(Me)SMe H 3-F H CH(Me)CH₂SMe H 3-F H CH₂CH₂S(═O)Me H 3-F HCH₂CH₂S(O)₂Me H 3-F H CH₂CO₂Me H 3-F H CH(Me)CO₂Me H 3-F H CH₂C(═O)Me H3-F H CH₂CH₂C(═O)Me H 3-F H 2-pyrazinyl 3-Cl 5-F H 2-thiazolyl 3-Cl 5-FH 2-oxazolyl 3-Cl 5-F H 2-chloro-2-propenyl 3-Cl 5-F H3,3-dichloro-2-propenyl 3-Cl 5-F H CH₂-2-tetrahydrofuranyl 3-Cl 5-F HCH₂-2-tetrahydropyranyl 3-Cl 5-F H CH₂CH₂OH 3-Cl 5-F H CH₂OMe 3-Cl 5-F HCH₂CH₂OMe 3-Cl 5-F H CH₂CH₂CH₂OMe 3-Cl 5-F H CH₂CH(Me)OMe 3-Cl 5-F HCH(Me)OMe 3-Cl 5-F H CH(Me)OEt 3-Cl 5-F H CH(Me)CH₂OMe 3-Cl 5-F HC(Me)₂CH₂OMe 3-Cl 5-F H CH(Me)CH₂CH₂OMe 3-Cl 5-F H (R)—CH(Me)CH₂OMe 3-Cl5-F H (S)—CH(Me)CH₂OMe 3-Cl 5-F H CH(Me)CH₂OH 3-Cl 5-F HCH(Me)CH₂OC(═O)Me 3-Cl 5-F H CH(Me)CH(OMe)₂ 3-Cl 5-F H CH₂-2-dioxolanyl3-Cl 5-F H CH₂CH₂OCF₃ 3-Cl 5-F H CH₂CH(Me)SMe 3-Cl 5-F H CH(Me)CH₂SMe3-Cl 5-F H CH₂CH₂S(═O)Me 3-Cl 5-F H CH₂CH₂S(O)₂Me 3-Cl 5-F H CH₂CO₂Me3-Cl 5-F H CH(Me)CO₂Me 3-Cl 5-F H CH₂C(═O)Me 3-Cl 5-F H CH₂CH₂C(═O)Me3-Cl 5-F H CH₂SiMe₃ H 3-F H CH₂CH₂SiMe₃ H 3-F H CH₂-2-thienyl H 3-F HCH₂-2-pyridinyl H 3-F H CH₂-3-pyridinyl H 3-F H NH₂ H 3-F H NHCH₃ H 3-FH NHCH₂CF₃ H 3-F H NHCH₂CH₃ H 3-F H NHCH(Me)CH₃ H 3-F H NHCH₂CH(Me)₂ H3-F H NHC(Me)₃ H 3-F H N(CH₃)₂ H 3-F H N(CH₃)CH₂CH₃ H 3-F HN(CH₂CH₃)CH₂CH₃ H 3-F H Me 3-F 4-F H Et 3-F 4-F H i-Pr 3-F 4-F H n-Pr3-F 4-F H i-Bu 3-F 4-F H n-Bu 3-F 4-F H s-Bu 3-F 4-F H t-butyl 3-F 4-F Hn-Hex 3-F 4-F H cyclopropyl 3-F 4-F H cyclopentyl 3-F 4-F H cyclohexyl3-F 4-F H 2-cyclohexenyl 3-F 4-F H 3-cyclohexenyl 3-F 4-F H CH₂-c-Pr 3-F4-F H 4-tetrahydropyranyl 3-F 4-F H CH₂SiMe₃ 3-Cl 5-F H CH₂CH₂SiMe₃ 3-Cl5-F H CH₂-2-thienyl 3-Cl 5-F H CH₂-2-pyridinyl 3-Cl 5-F HCH₂-3-pyridinyl 3-Cl 5-F H NH₂ 3-Cl 5-F H NHCH₃ 3-Cl 5-F H NHCH₂CF₃ 3-Cl5-F H NHCH₂CH₃ 3-Cl 5-F H NHCH(Me)CH₃ 3-Cl 5-F H NHCH₂CH(Me)₂ 3-Cl 5-F HNHC(Me)₃ 3-Cl 5-F H N(CH₃)₂ 3-Cl 5-F H N(CH₃)CH₂CH₃ 3-Cl 5-F HN(CH₂CH₃)CH₂CH₃ 3-Cl 5-F H Me 3-F 5-F H Et 3-F 5-F H i-Pr 3-F 5-F H n-Pr3-F 5-F H i-Bu 3-F 5-F H n-Bu 3-F 5-F H s-Bu 3-F 5-F H t-butyl 3-F 5-F Hn-Hex 3-F 5-F H cyclopropyl 3-F 5-F H cyclopentyl 3-F 5-F H cyclohexyl3-F 5-F H 2-cyclohexenyl 3-F 5-F H 3-cyclohexenyl 3-F 5-F H CH₂-c-Pr 3-F5-F H 4-tetrahydropyranyl 3-F 5-F H 3-tetrahydropyranyl 3-F 4-F H(R)-3-tetrahydropyranyl 3-F 4-F H (S)-3-tetrahydropyranyl 3-F 4-F H3-tetrahydrofuranyl 3-F 4-F H (R)-3-tetrahydrofuranyl 3-F 4-F H(S)-3-tetrahydrofuranyl 3-F 4-F H Ph 3-F 4-F H 2-Cl-phenyl 3-F 4-F H3-Cl-phenyl 3-F 4-F H 4-Cl-phenyl 3-F 4-F H 2-pyridinyl 3-F 4-F H2-pyrimidinyl 3-F 4-F H 2-pyrazinyl 3-F 4-F H 2-thiazolyl 3-F 4-F H2-oxazolyl 3-F 4-F H 2-chloro-2-propenyl 3-F 4-F H3,3-dichloro-2-propenyl 3-F 4-F H CH₂-2-tetrahydrofuranyl 3-F 4-F HCH₂-2-tetrahydropyranyl 3-F 4-F H CH₂CH₂OH 3-F 4-F H CH₂OMe 3-F 4-F HCH₂CH₂OMe 3-F 4-F H CH₂CH₂CH₂OMe 3-F 4-F H CH₂CH(Me)OMe 3-F 4-F HCH(Me)OMe 3-F 4-F H CH(Me)OEt 3-F 4-F H CH(Me)CH₂OMe 3-F 4-F HC(Me)₂CH₂OMe 3-F 4-F H CH(Me)CH₂CH₂OMe 3-F 4-F H (R)—CH(Me)CH₂OMe 3-F4-F H (S)—CH(Me)CH₂OMe 3-F 4-F H 3-tetrahydropyranyl 3-F 5-F H(R)-3-tetrahydropyranyl 3-F 5-F H (S)-3-tetrahydropyranyl 3-F 5-F H3-tetrahydrofuranyl 3-F 5-F H (R)-3-tetrahydrofuranyl 3-F 5-F H(S)-3-tetrahydrofuranyl 3-F 5-F H Ph 3-F 5-F H 2-Cl-phenyl 3-F 5-F H3-Cl-phenyl 3-F 5-F H 4-Cl-phenyl 3-F 5-F H 2-pyridinyl 3-F 5-F H2-pyrimidinyl 3-F 5-F H 2-pyrazinyl 3-F 5-F H 2-thiazolyl 3-F 5-F H2-oxazolyl 3-F 5-F H 2-chloro-2-propenyl 3-F 5-F H3,3-dichloro-2-propenyl 3-F 5-F H CH₂-2-tetrahydrofuranyl 3-F 5-F HCH₂-2-tetrahydropyranyl 3-F 5-F H CH₂CH₂OH 3-F 5-F H CH₂OMe 3-F 5-F HCH₂CH₂OMe 3-F 5-F H CH₂CH₂CH₂OMe 3-F 5-F H CH₂CH(Me)OMe 3-F 5-F HCH(Me)OMe 3-F 5-F H CH(Me)OEt 3-F 5-F H CH(Me)CH₂OMe 3-F 5-F HC(Me)₂CH₂OMe 3-F 5-F H CH(Me)CH₂CH₂OMe 3-F 5-F H (R)—CH(Me)CH₂OMe 3-F5-F H (S)—CH(Me)CH₂OMe 3-F 5-F H CH(Me)CH₂OH 3-F 4-F H CH(Me)CH₂OC(═O)Me3-F 4-F H CH(Me)CH(OMe)₂ 3-F 4-F H CH₂-2-dioxolanyl 3-F 4-F H CH₂CH₂OCF₃3-F 4-F H CH₂CH(Me)SMe 3-F 4-F H CH(Me)CH₂SMe 3-F 4-F H CH₂CH₂S(═O)Me3-F 4-F H CH₂CH₂S(O)₂Me 3-F 4-F H CH₂CO₂Me 3-F 4-F H CH(Me)CO₂Me 3-F 4-FH CH₂C(═O)Me 3-F 4-F H CH₂CH₂C(═O)Me 3-F 4-F H CH₂SiMe₃ 3-F 4-F HCH₂CH₂SiMe₃ 3-F 4-F H CH₂-2-thienyl 3-F 4-F H CH₂-2-pyridinyl 3-F 4-F HCH₂-3-pyridinyl 3-F 4-F H NH₂ 3-F 4-F H NHCH₃ 3-F 4-F H NHCH₂CF₃ 3-F 4-FH NHCH₂CH₃ 3-F 4-F H NHCH(Me)CH₃ 3-F 4-F H NHCH₂CH(Me)₂ 3-F 4-F HNHC(Me)₃ 3-F 4-F H N(CH₃)₂ 3-F 4-F H N(CH₃)CH₂CH₃ 3-F 4-F HN(CH₂CH₃)CH₂CH₃ 3-F 4-F H Me H 3-Cl H Et H 3-Cl H i-Pr H 3-Cl H n-Pr H3-Cl H i-Bu H 3-Cl H n-Bu H 3-Cl H s-Bu H 3-Cl H CH(Me)CH₂OH 3-F 5-F HCH(Me)CH₂OC(═O)Me 3-F 5-F H CH(Me)CH(OMe)₂ 3-F 5-F H CH₂-2-dioxolanyl3-F 5-F H CH₂CH₂OCF₃ 3-F 5-F H CH₂CH(Me)SMe 3-F 5-F H CH(Me)CH₂SMe 3-F5-F H CH₂CH₂S(═O)Me 3-F 5-F H CH₂CH₂S(O)₂Me 3-F 5-F H CH₂CO₂Me 3-F 5-F HCH(Me)CO₂Me 3-F 5-F H CH₂C(═O)Me 3-F 5-F H CH₂CH₂C(═O)Me 3-F 5-F HCH₂SiMe₃ 3-F 5-F H CH₂CH₂SiMe₃ 3-F 5-F H CH₂-2-thienyl 3-F 5-F HCH₂-2-pyridinyl 3-F 5-F H CH₂-3-pyridinyl 3-F 5-F H NH₂ 3-F 5-F H NHCH₃3-F 5-F H NHCH₂CF₃ 3-F 5-F H NHCH₂CH₃ 3-F 5-F H NHCH(Me)CH₃ 3-F 5-F HNHCH₂CH(Me)₂ 3-F 5-F H NHC(Me)₃ 3-F 5-F H N(CH₃)₂ 3-F 5-F H N(CH₃)CH₂CH₃3-F 5-F H N(CH₂CH₃)CH₂CH₃ 3-F 5-F H Me 3-CN 5-F H Et 3-CN 5-F H i-Pr3-CN 5-F H n-Pr 3-CN 5-F H i-Bu 3-CN 5-F H n-Bu 3-CN 5-F H s-Bu 3-CN 5-FH t-butyl H 3-Cl H n-Hex H 3-Cl H cyclopropyl H 3-Cl H cyclopentyl H3-Cl H cyclohexyl H 3-Cl H 2-cyclohexenyl H 3-Cl H 3-cyclohexenyl H 3-ClH CH₂-c-Pr H 3-Cl H 4-tetrahydropyranyl H 3-Cl H 3-tetrahydropyranyl H3-Cl H (R)-3-tetrahydropyranyl H 3-Cl H (S)-3-tetrahydropyranyl H 3-Cl H3-tetrahydrofuranyl H 3-Cl H (R)-3-tetrahydrofuranyl H 3-Cl H(S)-3-tetrahydrofuranyl H 3-Cl H Ph H 3-Cl H 2-Cl-phenyl H 3-Cl H3-Cl-phenyl H 3-Cl H 4-Cl-phenyl H 3-Cl H 2-pyridinyl H 3-Cl H2-pyrimidinyl H 3-Cl H 2-pyrazinyl H 3-Cl H 2-thiazolyl H 3-Cl H2-oxazolyl H 3-Cl H 2-chloro-2-propenyl H 3-Cl H 3,3-dichloro-2-propenylH 3-Cl H CH₂-2-tetrahydrofuranyl H 3-Cl H CH₂-2-tetrahydropyranyl H 3-ClH CH₂CH₂OH H 3-Cl H CH₂OMe H 3-Cl H CH₂CH₂OMe H 3-Cl H CH₂CH₂CH₂OMe H3-Cl H CH₂CH(Me)OMe H 3-Cl H CH(Me)OMe H 3-Cl H CH(Me)OEt H 3-Cl HCH(Me)CH₂OMe H 3-Cl H C(Me)₂CH₂OMe H 3-Cl H t-butyl 3-CN 5-F H n-Hex3-CN 5-F H cyclopropyl 3-CN 5-F H cyclopentyl 3-CN 5-F H cyclohexyl 3-CN5-F H 2-cyclohexenyl 3-CN 5-F H 3-cyclohexenyl 3-CN 5-F H CH₂-c-Pr 3-CN5-F H 4-tetrahydropyranyl 3-CN 5-F H 3-tetrahydropyranyl 3-CN 5-F H(R)-3-tetrahydropyranyl 3-CN 5-F H (S)-3-tetrahydropyranyl 3-CN 5-F H3-tetrahydrofuranyl 3-CN 5-F H (R)-3-tetrahydrofuranyl 3-CN 5-F H(S)-3-tetrahydrofuranyl 3-CN 5-F H Ph 3-CN 5-F H 2-Cl-phenyl 3-CN 5-F H3-Cl-phenyl 3-CN 5-F H 4-Cl-phenyl 3-CN 5-F H 2-pyridinyl 3-CN 5-F H2-pyrimidinyl 3-CN 5-F H 2-pyrazinyl 3-CN 5-F H 2-thiazolyl 3-CN 5-F H2-oxazolyl 3-CN 5-F H 2-chloro-2-propenyl 3-CN 5-F H3,3-dichloro-2-propenyl 3-CN 5-F H CH₂-2-tetrahydrofuranyl 3-CN 5-F HCH₂-2-tetrahydropyranyl 3-CN 5-F H CH₂CH₂OH 3-CN 5-F H CH₂OMe 3-CN 5-F HCH₂CH₂OMe 3-CN 5-F H CH₂CH₂CH₂OMe 3-CN 5-F H CH₂CH(Me)OMe 3-CN 5-F HCH(Me)OMe 3-CN 5-F H CH(Me)OEt 3-CN 5-F H CH(Me)CH₂OMe 3-CN 5-F HC(Me)₂CH₂OMe 3-CN 5-F H CH(Me)CH₂CH₂OMe H 3-Cl H (R)—CH(Me)CH₂OMe H 3-ClH (S)—CH(Me)CH₂OMe H 3-Cl H CH(Me)CH₂OH H 3-Cl H CH(Me)CH₂OC(═O)Me H3-Cl H CH(Me)CH(OMe)₂ H 3-Cl H CH₂-2-dioxolanyl H 3-Cl H CH₂CH₂OCF₃ H3-Cl H CH₂CH(Me)SMe H 3-Cl H CH(Me)CH₂SMe H 3-Cl H CH₂CH₂S(═O)Me H 3-ClH CH₂CH₂S(O)2Me H 3-Cl H CH₂CO₂Me H 3-Cl H CH(Me)CO₂Me H 3-Cl HCH₂C(═O)Me H 3-Cl H CH₂CH₂C(═O)Me H 3-Cl H CH₂SiMe₃ H 3-Cl H CH₂CH₂SiMe₃H 3-Cl H CH₂-2-thienyl H 3-Cl H CH₂-2-pyridinyl H 3-Cl H CH₂-3-pyridinylH 3-Cl H NH₂ H 3-Cl H NHCH₃ H 3-Cl H NHCH₂CF₃ H 3-Cl H NHCH₂CH₃ H 3-Cl HNHCH(Me)CH₃ H 3-Cl H NHCH₂CH(Me)₂ H 3-Cl H NHC(Me)₃ H 3-Cl H N(CH₃)₂ H3-Cl H N(CH₃)CH₂CH₃ H 3-Cl H N(CH₂CH₃)CH₂CH₃ H 3-Cl H Me H 3-CN H Et H3-CN H i-Pr H 3-CN H n-Pr H 3-CN H i-Bu H 3-CN H n-Bu H 3-CN HCH(Me)CH₂CH₂OMe 3-CN 5-F H (R)—CH(Me)CH₂OMe 3-CN 5-F H (S)—CH(Me)CH₂OMe3-CN 5-F H CH(Me)CH₂OH 3-CN 5-F H CH(Me)CH₂OC(═O)Me 3-CN 5-F HCH(Me)CH(OMe)₂ 3-CN 5-F H CH₂-2-dioxolanyl 3-CN 5-F H CH₂CH₂OCF₃ 3-CN5-F H CH₂CH(Me)SMe 3-CN 5-F H CH(Me)CH₂SMe 3-CN 5-F H CH₂CH₂S(═O)Me 3-CN5-F H CH₂CH₂S(O)2Me 3-CN 5-F H CH₂CO₂Me 3-CN 5-F H CH(Me)CO₂Me 3-CN 5-FH CH₂C(═O)Me 3-CN 5-F H CH₂CH₂C(═O)Me 3-CN 5-F H CH₂SiMe₃ 3-CN 5-F HCH₂CH₂SiMe₃ 3-CN 5-F H CH₂-2-thienyl 3-CN 5-F H CH₂-2-pyridinyl 3-CN 5-FH CH₂-3-pyridinyl 3-CN 5-F H NH₂ 3-CN 5-F H NHCH₃ 3-CN 5-F H NHCH₂CF₃3-CN 5-F H NHCH₂CH₃ 3-CN 5-F H NHCH(Me)CH₃ 3-CN 5-F H NHCH₂CH(Me)₂ 3-CN5-F H NHC(Me)₃ 3-CN 5-F H N(CH₃)₂ 3-CN 5-F H N(CH₃)CH₂CH₃ 3-CN 5-F HN(CH₂CH₃)CH₂CH₃ 3-CN 5-F H Me H 3-NO₂ H Et H 3-NO₂ H i-Pr H 3-NO₂ H n-PrH 3-NO₂ H i-Bu H 3-NO₂ H n-Bu H 3-NO₂ H s-Bu H 3-CN H t-butyl H 3-CN Hn-Hex H 3-CN H cyclopropyl H 3-CN H cyclopentyl H 3-CN H cyclohexyl H3-CN H 2-cyclohexenyl H 3-CN H 3-cyclohexenyl H 3-CN H CH₂-c-Pr H 3-CN H4-tetrahydropyranyl H 3-CN H 3-tetrahydropyranyl H 3-CN H(R)-3-tetrahydropyranyl H 3-CN H (S)-3-tetrahydropyranyl H 3-CN H3-tetrahydrofuranyl H 3-CN H (R)-3-tetrahydrofuranyl H 3-CN H(S)-3-tetrahydrofuranyl H 3-CN H Ph H 3-CN H 2-Cl-phenyl H 3-CN H3-Cl-phenyl H 3-CN H 4-Cl-phenyl H 3-CN H 2-pyridinyl H 3-CN H2-pyrimidinyl H 3-CN H 2-pyrazinyl H 3-CN H 2-thiazolyl H 3-CN H2-oxazolyl H 3-CN H 2-chloro-2-propenyl H 3-CN H 3,3-dichloro-2-propenylH 3-CN H CH₂-2-tetrahydrofuranyl H 3-CN H CH₂-2-tetrahydropyranyl H 3-CNH CH₂CH₂OH H 3-CN H CH₂OMe H 3-CN H CH₂CH₂OMe H 3-CN H CH₂CH₂CH₂OMe H3-CN H CH₂CH(Me)OMe H 3-CN H CH(Me)OMe H 3-CN H CH(Me)OEt H 3-CN HCH(Me)CH₂OMe H 3-CN H s-Bu H 3-NO₂ H t-butyl H 3-NO₂ H n-Hex H 3-NO₂ Hcyclopropyl H 3-NO₂ H cyclopentyl H 3-NO₂ H cyclohexyl H 3-NO₂ H2-cyclohexenyl H 3-NO₂ H 3-cyclohexenyl H 3-NO₂ H CH₂-c-Pr H 3-NO₂ H4-tetrahydropyranyl H 3-NO₂ H 3-tetrahydropyranyl H 3-NO₂ H(R)-3-tetrahydropyranyl H 3-NO₂ H (S)-3-tetrahydropyranyl H 3-NO₂ H3-tetrahydrofuranyl H 3-NO₂ H (R)-3-tetrahydrofuranyl H 3-NO₂ H(S)-3-tetrahydrofuranyl H 3-NO₂ H Ph H 3-NO₂ H 2-Cl-phenyl H 3-NO₂ H3-Cl-phenyl H 3-NO₂ H 4-Cl-phenyl H 3-NO₂ H 2-pyridinyl H 3-NO₂ H2-pyrimidinyl H 3-NO₂ H 2-pyrazinyl H 3-NO₂ H 2-thiazolyl H 3-NO₂ H2-oxazolyl H 3-NO₂ H 2-chloro-2-propenyl H 3-NO₂ H3,3-dichloro-2-propenyl H 3-NO₂ H CH₂-2-tetrahydrofuranyl H 3-NO₂ HCH₂-2-tetrahydropyranyl H 3-NO₂ H CH₂CH₂OH H 3-NO₂ H CH₂OMe H 3-NO₂ HCH₂CH₂OMe H 3-NO₂ H CH₂CH₂CH₂OMe H 3-NO₂ H CH₂CH(Me)OMe H 3-NO₂ HCH(Me)OMe H 3-NO₂ H CH(Me)OEt H 3-NO₂ H CH(Me)CH₂OMe H 3-NO₂ HC(Me)₂CH₂OMe H 3-CN H CH(Me)CH₂CH₂OMe H 3-CN H (R)—CH(Me)CH₂OMe H 3-CN H(S)—CH(Me)CH₂OMe H 3-CN H CH(Me)CH₂OH H 3-CN H CH(Me)CH₂OC(═O)Me H 3-CNH CH(Me)CH(OMe)₂ H 3-CN H CH₂-2-dioxolanyl H 3-CN H CH₂CH₂OCF₃ H 3-CN HCH₂CH(Me)SMe H 3-CN H CH(Me)CH₂SMe H 3-CN H CH₂CH₂S(═O)Me H 3-CN HCH₂CH₂S(O)₂Me H 3-CN H CH₂CO₂Me H 3-CN H CH(Me)CO₂Me H 3-CN H CH₂C(═O)MeH 3-CN H CH₂CH₂C(═O)Me H 3-CN H CH₂SiMe₃ H 3-CN H CH₂CH₂SiMe₃ H 3-CN HCH₂-2-thienyl H 3-CN H CH₂-2-pyridinyl H 3-CN H CH₂-3-pyridinyl H 3-CN HNH₂ H 3-CN H NHCH₃ H 3-CN H NHCH₂CF₃ H 3-CN H NHCH₂CH₃ H 3-CN HNHCH(Me)CH₃ H 3-CN H NHCH₂CH(Me)₂ H 3-CN H NHC(Me)₃ H 3-CN H N(CH₃)₂ H3-CN H N(CH₃)CH₂CH₃ H 3-CN H N(CH₂CH₃)CH₂CH₃ H 3-CN H Me H 3-Br H Et H3-Br H i-Pr H 3-Br H n-Pr H 3-Br H i-Bu H 3-Br H C(Me)₂CH₂OMe H 3-NO₂ HCH(Me)CH₂CH₂OMe H 3-NO₂ H (R)—CH(Me)CH₂OMe H 3-NO₂ H (S)—CH(Me)CH₂OMe H3-NO₂ H CH(Me)CH₂OH H 3-NO₂ H CH(Me)CH₂OC(═O)Me H 3-NO₂ H CH(Me)CH(OMe)₂H 3-NO₂ H CH₂-2-dioxolanyl H 3-NO₂ H CH₂CH₂OCF₃ H 3-NO₂ H CH₂CH(Me)SMe H3-NO₂ H CH(Me)CH₂SMe H 3-NO₂ H CH₂CH₂S(═O)Me H 3-NO₂ H CH₂CH₂S(O)₂Me H3-NO₂ H CH₂CO₂Me H 3-NO₂ H CH(Me)CO₂Me H 3-NO₂ H CH₂C(═O)Me H 3-NO₂ HCH₂CH₂C(═O)Me H 3-NO₂ H CH₂SiMe₃ H 3-NO₂ H CH₂CH₂SiMe₃ H 3-NO₂ HCH₂-2-thienyl H 3-NO₂ H CH₂-2-pyridinyl H 3-NO₂ H CH₂-3-pyridinyl H3-NO₂ H NH₂ H 3-NO₂ H NHCH₃ H 3-NO₂ H NHCH₂CF₃ H 3-NO₂ H NHCH₂CH₃ H3-NO₂ H NHCH(Me)CH₃ H 3-NO₂ H NHCH₂CH(Me)₂ H 3-NO₂ H NHC(Me)₃ H 3-NO₂ HN(CH₃)₂ H 3-NO₂ H N(CH₃)CH₂CH₃ H 3-NO₂ H N(CH₂CH₃)CH₂CH₃ H 3-NO₂ H Me H3-I H Et H 3-I H i-Pr H 3-I H n-Pr H 3-I H i-Bu H 3-I H n-Bu H 3-Br Hs-Bu H 3-Br H t-butyl H 3-Br H n-Hex H 3-Br H cyclopropyl H 3-Br Hcyclopentyl H 3-Br H cyclohexyl H 3-Br H 2-cyclohexenyl H 3-Br H3-cyclohexenyl H 3-Br H CH₂-c-Pr H 3-Br H 4-tetrahydropyranyl H 3-Br H3-tetrahydropyranyl H 3-Br H (R)-3-tetrahydropyranyl H 3-Br H(S)-3-tetrahydropyranyl H 3-Br H 3-tetrahydrofuranyl H 3-Br H(R)-3-tetrahydrofuranyl H 3-Br H (S)-3-tetrahydrofuranyl H 3-Br H Ph H3-Br H 2-Cl-phenyl H 3-Br H 3-Cl-phenyl H 3-Br H 4-Cl-phenyl H 3-Br H2-pyridinyl H 3-Br H 2-pyrimidinyl H 3-Br H 2-pyrazinyl H 3-Br H2-thiazolyl H 3-Br H 2-oxazolyl H 3-Br H 2-chloro-2-propenyl H 3-Br H3,3-dichloro-2-propenyl H 3-Br H CH₂-2-tetrahydrofuranyl H 3-Br HCH₂-2-tetrahydropyranyl H 3-Br H CH₂CH₂OH H 3-Br H CH₂OMe H 3-Br HCH₂CH₂OMe H 3-Br H CH₂CH₂CH₂OMe H 3-Br H CH₂CH(Me)OMe H 3-Br H CH(Me)OMeH 3-Br H CH(Me)OEt H 3-Br H n-Bu H 3-I H s-Bu H 3-I H t-butyl H 3-I Hn-Hex H 3-I H cyclopropyl H 3-I H cyclopentyl H 3-I H cyclohexyl H 3-I H2-cyclohexenyl H 3-I H 3-cyclohexenyl H 3-I H CH₂-c-Pr H 3-I H4-tetrahydropyranyl H 3-I H 3-tetrahydropyranyl H 3-I H(R)-3-tetrahydropyranyl H 3-I H (S)-3-tetrahydropyranyl H 3-I H3-tetrahydrofuranyl H 3-I H (R)-3-tetrahydrofuranyl H 3-I H(S)-3-tetrahydrofuranyl H 3-I H Ph H 3-I H 2-Cl-phenyl H 3-I H3-Cl-phenyl H 3-I H 4-Cl-phenyl H 3-I H 2-pyridinyl H 3-I H2-pyrimidinyl H 3-I H 2-pyrazinyl H 3-I H 2-thiazolyl H 3-I H 2-oxazolylH 3-I H 2-chloro-2-propenyl H 3-I H 3,3-dichloro-2-propenyl H 3-I HCH₂-2-tetrahydrofuranyl H 3-I H CH₂-2-tetrahydropyranyl H 3-I H CH₂CH₂OHH 3-I H CH₂OMe H 3-I H CH₂CH₂OMe H 3-I H CH₂CH₂CH₂OMe H 3-I HCH₂CH(Me)OMe H 3-I H CH(Me)OMe H 3-I H CH(Me)OEt H 3-I H CH(Me)CH₂OMe H3-Br H C(Me)₂CH₂OMe H 3-Br H CH(Me)CH₂CH₂OMe H 3-Br H (R)—CH(Me)CH₂OMe H3-Br H (S)—CH(Me)CH₂OMe H 3-Br H CH(Me)CH₂OH H 3-Br H CH(Me)CH₂OC(═O)MeH 3-Br H CH(Me)CH(OMe)₂ H 3-Br H CH₂-2-dioxolanyl H 3-Br H CH₂CH₂OCF₃ H3-Br H CH₂CH(Me)SMe H 3-Br H CH(Me)CH₂SMe H 3-Br H CH₂CH₂S(═O)Me H 3-BrH CH₂CH₂S(O)₂Me H 3-Br H CH₂CO₂Me H 3-Br H CH(Me)CO₂Me H 3-Br HCH₂C(═O)Me H 3-Br H CH₂CH₂C(═O)Me H 3-Br H CH₂SiMe₃ H 3-Br H CH₂CH₂SiMe₃H 3-Br H CH₂-2-thienyl H 3-Br H CH₂-2-pyridinyl H 3-Br H CH₂-3-pyridinylH 3-Br H NH₂ H 3-Br H NHCH₃ H 3-Br H NHCH₂CF₃ H 3-Br H NHCH₂CH₃ H 3-Br HNHCH(Me)CH₃ H 3-Br H NHCH₂CH(Me)₂ H 3-Br H NHC(Me)₃ H 3-Br H N(CH₃)₂ H3-Br H N(CH₃)CH₂CH₃ H 3-Br H N(CH₂CH₃)CH₂CH₃ H 3-Br H Me H 3-Me H Et H3-Me H i-Pr H 3-Me H n-Pr H 3-Me H CH(Me)CH₂OMe H 3-I H C(Me)₂CH₂OMe H3-I H CH(Me)CH₂CH₂OMe H 3-I H (R)—CH(Me)CH₂OMe H 3-I H (S)—CH(Me)CH₂OMeH 3-I H CH(Me)CH₂OH H 3-I H CH(Me)CH₂OC(═O)Me H 3-I H CH(Me)CH(OMe)₂ H3-I H CH₂-2-dioxolanyl H 3-I H CH₂CH₂OCF₃ H 3-I H CH₂CH(Me)SMe H 3-I HCH(Me)CH₂SMe H 3-I H CH₂CH₂S(═O)Me H 3-I H CH₂CH₂S(O)₂Me H 3-I HCH₂CO₂Me H 3-I H CH(Me)CO₂Me H 3-I H CH₂C(═O)Me H 3-I H CH₂CH₂C(═O)Me H3-I H CH₂SiMe₃ H 3-I H CH₂CH₂SiMe₃ H 3-I H CH₂-2-thienyl H 3-I HCH₂-2-pyridinyl H 3-I H CH₂-3-pyridinyl H 3-I H NH₂ H 3-I H NHCH₃ H 3-IH NHCH₂CF₃ H 3-I H NHCH₂CH₃ H 3-I H NHCH(Me)CH₃ H 3-I H NHCH₂CH(Me)₂ H3-I H NHC(Me)₃ H 3-I H N(CH₃)₂ H 3-I H N(CH₃)CH₂CH₃ H 3-I HN(CH₂CH₃)CH₂CH₃ H 3-I H Me H 4-Me H Et H 4-Me H i-Pr H 4-Me H n-Pr H4-Me H i-Bu H 3-Me H n-Bu H 3-Me H s-Bu H 3-Me H t-butyl H 3-Me H n-HexH 3-Me H cyclopropyl H 3-Me H cyclopentyl H 3-Me H cyclohexyl H 3-Me H2-cyclohexenyl H 3-Me H 3-cyclohexenyl H 3-Me H CH₂-c-Pr H 3-Me H4-tetrahydropyranyl H 3-Me H 3-tetrahydropyranyl H 3-Me H(R)-3-tetrahydropyranyl H 3-Me H (S)-3-tetrahydropyranyl H 3-Me H3-tetrahydrofuranyl H 3-Me H (R)-3-tetrahydrofuranyl H 3-Me H(S)-3-tetrahydrofuranyl H 3-Me H Ph H 3-Me H 2-Cl-phenyl H 3-Me H3-Cl-phenyl H 3-Me H 4-Cl-phenyl H 3-Me H 2-pyridinyl H 3-Me H2-pyrimidinyl H 3-Me H 2-pyrazinyl H 3-Me H 2-thiazolyl H 3-Me H2-oxazolyl H 3-Me H 2-chloro-2-propenyl H 3-Me H 3,3-dichloro-2-propenylH 3-Me H CH₂-2-tetrahydrofuranyl H 3-Me H CH₂-2-tetrahydropyranyl H 3-MeH CH₂CH₂OH H 3-Me H CH₂OMe H 3-Me H CH₂CH₂OMe H 3-Me H CH₂CH₂CH₂OMe H3-Me H CH₂CH(Me)OMe H 3-Me H CH(Me)OMe H 3-Me H i-Bu H 4-Me H n-Bu H4-Me H s-Bu H 4-Me H t-butyl H 4-Me H n-Hex H 4-Me H cyclopropyl H 4-MeH cyclopentyl H 4-Me H cyclohexyl H 4-Me H 2-cyclohexenyl H 4-Me H3-cyclohexenyl H 4-Me H CH₂-c-Pr H 4-Me H 4-tetrahydropyranyl H 4-Me H3-tetrahydropyranyl H 4-Me H (R)-3-tetrahydropyranyl H 4-Me H(S)-3-tetrahydropyranyl H 4-Me H 3-tetrahydrofuranyl H 4-Me H(R)-3-tetrahydrofuranyl H 4-Me H (S)-3-tetrahydrofuranyl H 4-Me H Ph H4-Me H 2-Cl-phenyl H 4-Me H 3-Cl-phenyl H 4-Me H 4-Cl-phenyl H 4-Me H2-pyridinyl H 4-Me H 2-pyrimidinyl H 4-Me H 2-pyrazinyl H 4-Me H2-thiazolyl H 4-Me H 2-oxazolyl H 4-Me H 2-chloro-2-propenyl H 4-Me H3,3-dichloro-2-propenyl H 4-Me H CH₂-2-tetrahydrofuranyl H 4-Me HCH₂-2-tetrahydropyranyl H 4-Me H CH₂CH₂OH H 4-Me H CH₂OMe H 4-Me HCH₂CH₂OMe H 4-Me H CH₂CH₂CH₂OMe H 4-Me H CH₂CH(Me)OMe H 4-Me H CH(Me)OMeH 4-Me H CH(Me)OEt H 3-Me H CH(Me)CH₂OMe H 3-Me H C(Me)₂CH₂OMe H 3-Me HCH(Me)CH₂CH₂OMe H 3-Me H (R)—CH(Me)CH₂OMe H 3-Me H (S)—CH(Me)CH₂OMe H3-Me H CH(Me)CH₂OH H 3-Me H CH(Me)CH₂OC(═O)Me H 3-Me H CH(Me)CH(OMe)₂ H3-Me H CH₂-2-dioxolanyl H 3-Me H CH₂CH₂OCF₃ H 3-Me H CH₂CH(Me)SMe H 3-MeH CH(Me)CH₂SMe H 3-Me H CH₂CH₂S(═O)Me H 3-Me H CH₂CH₂S(O)₂Me H 3-Me HCH₂CO₂Me H 3-Me H CH(Me)CO₂Me H 3-Me H CH₂C(═O)Me H 3-Me H CH₂CH₂C(═O)MeH 3-Me H CH₂SiMe₃ H 3-Me H CH₂CH₂SiMe₃ H 3-Me H CH₂-2-thienyl H 3-Me HCH₂-2-pyridinyl H 3-Me H CH₂-3-pyridinyl H 3-Me H NH₂ H 3-Me H NHCH₃ H3-Me H NHCH₂CF₃ H 3-Me H NHCH₂CH₃ H 3-Me H NHCH(Me)CH₃ H 3-Me HNHCH₂CH(Me)₂ H 3-Me H NHC(Me)₃ H 3-Me H N(CH₃)₂ H 3-Me H N(CH₃)CH₂CH₃ H3-Me H N(CH₂CH₃)CH₂CH₃ H 3-Me H Me 3-F 4-Me H Et 3-F 4-Me H i-Pr 3-F4-Me H CH(Me)OEt H 4-Me H CH(Me)CH₂OMe H 4-Me H C(Me)₂CH₂OMe H 4-Me HCH(Me)CH₂CH₂OMe H 4-Me H (R)—CH(Me)CH₂OMe H 4-Me H (S)—CH(Me)CH₂OMe H4-Me H CH(Me)CH₂OH H 4-Me H CH(Me)CH₂OC(═O)Me H 4-Me H CH(Me)CH(OMe)₂ H4-Me H CH₂-2-dioxolanyl H 4-Me H CH₂CH₂OCF₃ H 4-Me H CH₂CH(Me)SMe H 4-MeH CH(Me)CH₂SMe H 4-Me H CH₂CH₂S(═O)Me H 4-Me H CH₂CH₂S(O)₂Me H 4-Me HCH₂CO₂Me H 4-Me H CH(Me)CO₂Me H 4-Me H CH₂C(═O)Me H 4-Me H CH₂CH₂C(═O)MeH 4-Me H CH₂SiMe₃ H 4-Me H CH₂CH₂SiMe₃ H 4-Me H CH₂-2-thienyl H 4-Me HCH₂-2-pyridinyl H 4-Me H CH₂-3-pyridinyl H 4-Me H NH₂ H 4-Me H NHCH₃ H4-Me H NHCH₂CF₃ H 4-Me H NHCH₂CH₃ H 4-Me H NHCH(Me)CH₃ H 4-Me HNHCH₂CH(Me)₂ H 4-Me H NHC(Me)₃ H 4-Me H N(CH₃)₂ H 4-Me H N(CH₃)CH₂CH₃ H4-Me H N(CH₂CH₃)CH₂CH₃ H 4-Me H Me 3-Me 4-Me H Et 3-Me 4-Me H i-Pr 3-Me4-Me H n-Pr 3-F 4-Me H i-Bu 3-F 4-Me H n-Bu 3-F 4-Me H s-Bu 3-F 4-Me Ht-butyl 3-F 4-Me H n-Hex 3-F 4-Me H cyclopropyl 3-F 4-Me H cyclopentyl3-F 4-Me H cyclohexyl 3-F 4-Me H 2-cyclohexenyl 3-F 4-Me H3-cyclohexenyl 3-F 4-Me H CH₂-c-Pr 3-F 4-Me H 4-tetrahydropyranyl 3-F4-Me H 3-tetrahydropyranyl 3-F 4-Me H (R)-3-tetrahydropyranyl 3-F 4-Me H(S)-3-tetrahydropyranyl 3-F 4-Me H 3-tetrahydrofuranyl 3-F 4-Me H(R)-3-tetrahydrofuranyl 3-F 4-Me H (S)-3-tetrahydrofuranyl 3-F 4-Me H Ph3-F 4-Me H 2-Cl-phenyl 3-F 4-Me H 3-Cl-phenyl 3-F 4-Me H 4-Cl-phenyl 3-F4-Me H 2-pyridinyl 3-F 4-Me H 2-pyrimidinyl 3-F 4-Me H 2-pyrazinyl 3-F4-Me H 2-thiazolyl 3-F 4-Me H 2-oxazolyl 3-F 4-Me H 2-chloro-2-propenyl3-F 4-Me H 3,3-dichloro-2-propenyl 3-F 4-Me H CH₂-2-tetrahydrofuranyl3-F 4-Me H CH₂-2-tetrahydropyranyl 3-F 4-Me H CH₂CH₂OH 3-F 4-Me H CH₂OMe3-F 4-Me H CH₂CH₂OMe 3-F 4-Me H CH₂CH₂CH₂OMe 3-F 4-Me H CH₂CH(Me)OMe 3-F4-Me H n-Pr 3-Me 4-Me H i-Bu 3-Me 4-Me H n-Bu 3-Me 4-Me H s-Bu 3-Me 4-MeH t-butyl 3-Me 4-Me H n-Hex 3-Me 4-Me H cyclopropyl 3-Me 4-Me Hcyclopentyl 3-Me 4-Me H cyclohexyl 3-Me 4-Me H 2-cyclohexenyl 3-Me 4-MeH 3-cyclohexenyl 3-Me 4-Me H CH₂-c-Pr 3-Me 4-Me H 4-tetrahydropyranyl3-Me 4-Me H 3-tetrahydropyranyl 3-Me 4-Me H (R)-3-tetrahydropyranyl 3-Me4-Me H (S)-3-tetrahydropyranyl 3-Me 4-Me H 3-tetrahydrofuranyl 3-Me 4-MeH (R)-3-tetrahydrofuranyl 3-Me 4-Me H (S)-3-tetrahydrofuranyl 3-Me 4-MeH Ph 3-Me 4-Me H 2-Cl-phenyl 3-Me 4-Me H 3-Cl-phenyl 3-Me 4-Me H4-Cl-phenyl 3-Me 4-Me H 2-pyridinyl 3-Me 4-Me H 2-pyrimidinyl 3-Me 4-MeH 2-pyrazinyl 3-Me 4-Me H 2-thiazolyl 3-Me 4-Me H 2-oxazolyl 3-Me 4-Me H2-chloro-2-propenyl 3-Me 4-Me H 3,3-dichloro-2-propenyl 3-Me 4-Me HCH₂-2-tetrahydrofuranyl 3-Me 4-Me H CH₂-2-tetrahydropyranyl 3-Me 4-Me HCH₂CH₂OH 3-Me 4-Me H CH₂OMe 3-Me 4-Me H CH₂CH₂OMe 3-Me 4-Me HCH₂CH₂CH₂OMe 3-Me 4-Me H CH₂CH(Me)OMe 3-Me 4-Me H CH(Me)OMe 3-F 4-Me HCH(Me)OEt 3-F 4-Me H CH(Me)CH₂OMe 3-F 4-Me H C(Me)₂CH₂OMe 3-F 4-Me HCH(Me)CH₂CH₂OMe 3-F 4-Me H (R)—CH(Me)CH₂OMe 3-F 4-Me H (S)—CH(Me)CH₂OMe3-F 4-Me H CH(Me)CH₂OH 3-F 4-Me H CH(Me)CH₂OC(═O)Me 3-F 4-Me HCH(Me)CH(OMe)₂ 3-F 4-Me H CH₂-2-dioxolanyl 3-F 4-Me H CH₂CH₂OCF₃ 3-F4-Me H CH₂CH(Me)SMe 3-F 4-Me H CH(Me)CH₂SMe 3-F 4-Me H CH₂CH₂S(═O)Me 3-F4-Me H CH₂CH₂S(O)₂Me 3-F 4-Me H CH₂CO₂Me 3-F 4-Me H CH(Me)CO₂Me 3-F 4-MeH CH₂C(═O)Me 3-F 4-Me H CH₂CH₂C(═O)Me 3-F 4-Me H CH₂SiMe₃ 3-F 4-Me HCH₂CH₂SiMe₃ 3-F 4-Me H CH₂-2-thienyl 3-F 4-Me H CH₂-2-pyridinyl 3-F 4-MeH CH₂-3-pyridinyl 3-F 4-Me H NH₂ 3-F 4-Me H NHCH₃ 3-F 4-Me H NHCH₂CF₃3-F 4-Me H NHCH₂CH₃ 3-F 4-Me H NHCH(Me)CH₃ 3-F 4-Me H NHCH₂CH(Me)₂ 3-F4-Me H NHC(Me)₃ 3-F 4-Me H N(CH₃)₂ 3-F 4-Me H N(CH₃)CH₂CH₃ 3-F 4-Me HN(CH₂CH₃)CH₂CH₃ 3-F 4-Me H Me 3-NO₂ 4-Me H Et 3-NO₂ 4-Me H CH(Me)OMe3-Me 4-Me H CH(Me)OEt 3-Me 4-Me H CH(Me)CH₂OMe 3-Me 4-Me H C(Me)₂CH₂OMe3-Me 4-Me H CH(Me)CH₂CH₂OMe 3-Me 4-Me H (R)—CH(Me)CH₂OMe 3-Me 4-Me H(S)—CH(Me)CH₂OMe 3-Me 4-Me H CH(Me)CH₂OH 3-Me 4-Me H CH(Me)CH₂OC(═O)Me3-Me 4-Me H CH(Me)CH(OMe)₂ 3-Me 4-Me H CH₂-2-dioxolanyl 3-Me 4-Me HCH₂CH₂OCF₃ 3-Me 4-Me H CH₂CH(Me)SMe 3-Me 4-Me H CH(Me)CH₂SMe 3-Me 4-Me HCH₂CH₂S(═O)Me 3-Me 4-Me H CH₂CH₂S(O)₂Me 3-Me 4-Me H CH₂CO₂Me 3-Me 4-Me HCH(Me)CO₂Me 3-Me 4-Me H CH₂C(═O)Me 3-Me 4-Me H CH₂CH₂C(═O)Me 3-Me 4-Me HCH₂SiMe₃ 3-Me 4-Me H CH₂CH₂SiMe₃ 3-Me 4-Me H CH₂-2-thienyl 3-Me 4-Me HCH₂-2-pyridinyl 3-Me 4-Me H CH₂-3-pyridinyl 3-Me 4-Me H NH₂ 3-Me 4-Me HNHCH₃ 3-Me 4-Me H NHCH₂CF₃ 3-Me 4-Me H NHCH₂CH₃ 3-Me 4-Me H NHCH(Me)CH₃3-Me 4-Me H NHCH₂CH(Me)₂ 3-Me 4-Me H NHC(Me)₃ 3-Me 4-Me H N(CH₃)₂ 3-Me4-Me H N(CH₃)CH₂CH₃ 3-Me 4-Me H N(CH₂CH₃)CH₂CH₃ 3-Me 4-Me H Me 3-Cl 5-ClH Et 3-Cl 5-Cl H i-Pr 3-NO₂ 4-Me H n-Pr 3-NO₂ 4-Me H i-Bu 3-NO₂ 4-Me Hn-Bu 3-NO₂ 4-Me H s-Bu 3-NO₂ 4-Me H t-butyl 3-NO₂ 4-Me H n-Hex 3-NO₂4-Me H cyclopropyl 3-NO₂ 4-Me H cyclopentyl 3-NO₂ 4-Me H cyclohexyl3-NO₂ 4-Me H 2-cyclohexenyl 3-NO₂ 4-Me H 3-cyclohexenyl 3-NO₂ 4-Me HCH₂-c-Pr 3-NO₂ 4-Me H 4-tetrahydropyranyl 3-NO₂ 4-Me H3-tetrahydropyranyl 3-NO₂ 4-Me H (R)-3-tetrahydropyranyl 3-NO₂ 4-Me H(S)-3-tetrahydropyranyl 3-NO₂ 4-Me H 3-tetrahydrofuranyl 3-NO₂ 4-Me H(R)-3-tetrahydrofuranyl 3-NO₂ 4-Me H (S)-3-tetrahydrofuranyl 3-NO₂ 4-MeH Ph 3-NO₂ 4-Me H 2-Cl-phenyl 3-NO₂ 4-Me H 3-Cl-phenyl 3-NO₂ 4-Me H4-Cl-phenyl 3-NO₂ 4-Me H 2-pyridinyl 3-NO₂ 4-Me H 2-pyrimidinyl 3-NO₂4-Me H 2-pyrazinyl 3-NO₂ 4-Me H 2-thiazolyl 3-NO₂ 4-Me H 2-oxazolyl3-NO₂ 4-Me H 2-chloro-2-propenyl 3-NO₂ 4-Me H 3,3-dichloro-2-propenyl3-NO₂ 4-Me H CH₂-2-tetrahydrofuranyl 3-NO₂ 4-Me HCH₂-2-tetrahydropyranyl 3-NO₂ 4-Me H CH₂CH₂OH 3-NO₂ 4-Me H CH₂OMe 3-NO₂4-Me H CH₂CH₂OMe 3-NO₂ 4-Me H CH₂CH₂CH₂OMe 3-NO₂ 4-Me H i-Pr 3-Cl 5-Cl Hn-Pr 3-Cl 5-Cl H i-Bu 3-Cl 5-Cl H n-Bu 3-Cl 5-Cl H s-Bu 3-Cl 5-Cl Ht-butyl 3-Cl 5-Cl H n-Hex 3-Cl 5-Cl H cyclopropyl 3-Cl 5-Cl Hcyclopentyl 3-Cl 5-Cl H cyclohexyl 3-Cl 5-Cl H 2-cyclohexenyl 3-Cl 5-ClH 3-cyclohexenyl 3-Cl 5-Cl H CH₂-c-Pr 3-Cl 5-Cl H 4-tetrahydropyranyl3-Cl 5-Cl H 3-tetrahydropyranyl 3-Cl 5-Cl H (R)-3-tetrahydropyranyl 3-Cl5-Cl H (S)-3-tetrahydropyranyl 3-Cl 5-Cl H 3-tetrahydrofuranyl 3-Cl 5-ClH (R)-3-tetrahydrofuranyl 3-Cl 5-Cl H (S)-3-tetrahydrofuranyl 3-Cl 5-ClH Ph 3-Cl 5-Cl H 2-Cl-phenyl 3-Cl 5-Cl H 3-Cl-phenyl 3-Cl 5-Cl H4-Cl-phenyl 3-Cl 5-Cl H 2-pyridinyl 3-Cl 5-Cl H 2-pyrimidinyl 3-Cl 5-ClH 2-pyrazinyl 3-Cl 5-Cl H 2-thiazolyl 3-Cl 5-Cl H 2-oxazolyl 3-Cl 5-Cl H2-chloro-2-propenyl 3-Cl 5-Cl H 3,3-dichloro-2-propenyl 3-Cl 5-Cl HCH₂-2-tetrahydrofuranyl 3-Cl 5-Cl H CH₂-2-tetrahydropyranyl 3-Cl 5-Cl HCH₂CH₂OH 3-Cl 5-Cl H CH₂OMe 3-Cl 5-Cl H CH₂CH₂OMe 3-Cl 5-Cl HCH₂CH₂CH₂OMe 3-Cl 5-Cl H CH₂CH(Me)OMe 3-NO₂ 4-Me H CH(Me)OMe 3-NO₂ 4-MeH CH(Me)OEt 3-NO₂ 4-Me H CH(Me)CH₂OMe 3-NO₂ 4-Me H C(Me)₂CH₂OMe 3-NO₂4-Me H CH(Me)CH₂CH₂OMe 3-NO₂ 4-Me H (R)—CH(Me)CH₂OMe 3-NO₂ 4-Me H(S)—CH(Me)CH₂OMe 3-NO₂ 4-Me H CH(Me)CH₂OH 3-NO₂ 4-Me H CH(Me)CH₂OC(═O)Me3-NO₂ 4-Me H CH(Me)CH(OMe)₂ 3-NO₂ 4-Me H CH₂-2-dioxolanyl 3-NO₂ 4-Me HCH₂CH₂OCF₃ 3-NO₂ 4-Me H CH₂CH(Me)SMe 3-NO₂ 4-Me H CH(Me)CH₂SMe 3-NO₂4-Me H CH₂CH₂S(═O)Me 3-NO₂ 4-Me H CH₂CH₂S(O)₂Me 3-NO₂ 4-Me H CH₂CO₂Me3-NO₂ 4-Me H CH(Me)CO₂Me 3-NO₂ 4-Me H CH₂C(═O)Me 3-NO₂ 4-Me HCH₂CH₂C(═O)Me 3-NO₂ 4-Me H CH₂SiMe₃ 3-NO₂ 4-Me H CH₂CH₂SiMe₃ 3-NO₂ 4-MeH CH₂-2-thienyl 3-NO₂ 4-Me H CH₂-2-pyridinyl 3-NO₂ 4-Me HCH₂-3-pyridinyl 3-NO₂ 4-Me H NH₂ 3-NO₂ 4-Me H NHCH₃ 3-NO₂ 4-Me HNHCH₂CF₃ 3-NO₂ 4-Me H NHCH₂CH₃ 3-NO₂ 4-Me H NHCH(Me)CH₃ 3-NO₂ 4-Me HNHCH₂CH(Me)₂ 3-NO₂ 4-Me H NHC(Me)₃ 3-NO₂ 4-Me H N(CH₃)₂ 3-NO₂ 4-Me HN(CH₃)CH₂CH₃ 3-NO₂ 4-Me H N(CH₂CH₃)CH₂CH₃ 3-NO₂ 4-Me H Me 3-Cl 5-CN HCH₂CH(Me)OMe 3-Cl 5-Cl H CH(Me)OMe 3-Cl 5-Cl H CH(Me)OEt 3-Cl 5-Cl HCH(Me)CH₂OMe 3-Cl 5-Cl H C(Me)₂CH₂OMe 3-Cl 5-Cl H CH(Me)CH₂CH₂OMe 3-Cl5-Cl H (R)—CH(Me)CH₂OMe 3-Cl 5-Cl H (S)—CH(Me)CH₂OMe 3-Cl 5-Cl HCH(Me)CH₂OH 3-Cl 5-Cl H CH(Me)CH₂OC(═O)Me 3-Cl 5-Cl H CH(Me)CH(OMe)₂3-Cl 5-Cl H CH₂-2-dioxolanyl 3-Cl 5-Cl H CH₂CH₂OCF₃ 3-Cl 5-Cl HCH₂CH(Me)SMe 3-Cl 5-Cl H CH(Me)CH₂SMe 3-Cl 5-Cl H CH₂CH₂S(═O)Me 3-Cl5-Cl H CH₂CH₂S(O)₂Me 3-Cl 5-Cl H CH₂CO₂Me 3-Cl 5-Cl H CH(Me)CO₂Me 3-Cl5-Cl H CH₂C(═O)Me 3-Cl 5-Cl H CH₂CH₂C(═O)Me 3-Cl 5-Cl H CH₂SiMe₃ 3-Cl5-Cl H CH₂CH₂SiMe₃ 3-Cl 5-Cl H CH₂-2-thienyl 3-Cl 5-Cl H CH₂-2-pyridinyl3-Cl 5-Cl H CH₂-3-pyridinyl 3-Cl 5-Cl H NH₂ 3-Cl 5-Cl H NHCH₃ 3-Cl 5-ClH NHCH₂CF₃ 3-Cl 5-Cl H NHCH₂CH₃ 3-Cl 5-Cl H NHCH(Me)CH₃ 3-Cl 5-Cl HNHCH₂CH(Me)₂ 3-Cl 5-Cl H NHC(Me)₃ 3-Cl 5-Cl H N(CH₃)₂ 3-Cl 5-Cl HN(CH₃)CH₂CH₃ 3-Cl 5-Cl H N(CH₂CH₃)CH₂CH₃ 3-Cl 5-Cl H Me 3-F 4-Cl H Et3-Cl 5-CN H i-Pr 3-Cl 5-CN H n-Pr 3-Cl 5-CN H i-Bu 3-Cl 5-CN H n-Bu 3-Cl5-CN H s-Bu 3-Cl 5-CN H t-butyl 3-Cl 5-CN H n-Hex 3-Cl 5-CN Hcyclopropyl 3-Cl 5-CN H cyclopentyl 3-Cl 5-CN H cyclohexyl 3-Cl 5-CN H2-cyclohexenyl 3-Cl 5-CN H 3-cyclohexenyl 3-Cl 5-CN H CH₂-c-Pr 3-Cl 5-CNH 4-tetrahydropyranyl 3-Cl 5-CN H 3-tetrahydropyranyl 3-Cl 5-CN H(R)-3-tetrahydropyranyl 3-Cl 5-CN H (S)-3-tetrahydropyranyl 3-Cl 5-CN H3-tetrahydrofuranyl 3-Cl 5-CN H (R)-3-tetrahydrofuranyl 3-Cl 5-CN H(S)-3-tetrahydrofuranyl 3-Cl 5-CN H Ph 3-Cl 5-CN H 2-Cl-phenyl 3-Cl 5-CNH 3-Cl-phenyl 3-Cl 5-CN H 4-Cl-phenyl 3-Cl 5-CN H 2-pyridinyl 3-Cl 5-CNH 2-pyrimidinyl 3-Cl 5-CN H 2-pyrazinyl 3-Cl 5-CN H 2-thiazolyl 3-Cl5-CN H 2-oxazolyl 3-Cl 5-CN H 2-chloro-2-propenyl 3-Cl 5-CN H3,3-dichloro-2-propenyl 3-Cl 5-CN H CH₂-2-tetrahydrofuranyl 3-Cl 5-CN HCH₂-2-tetrahydropyranyl 3-Cl 5-CN H CH₂CH₂OH 3-Cl 5-CN H CH₂OMe 3-Cl5-CN H CH₂CH₂OMe 3-Cl 5-CN H Et 3-F 4-Cl H i-Pr 3-F 4-Cl H n-Pr 3-F 4-ClH i-Bu 3-F 4-Cl H n-Bu 3-F 4-Cl H s-Bu 3-F 4-Cl H t-butyl 3-F 4-Cl Hn-Hex 3-F 4-Cl H cyclopropyl 3-F 4-Cl H cyclopentyl 3-F 4-Cl Hcyclohexyl 3-F 4-Cl H 2-cyclohexenyl 3-F 4-Cl H 3-cyclohexenyl 3-F 4-ClH CH₂-c-Pr 3-F 4-Cl H 4-tetrahydropyranyl 3-F 4-Cl H 3-tetrahydropyranyl3-F 4-Cl H (R)-3-tetrahydropyranyl 3-F 4-Cl H (S)-3-tetrahydropyranyl3-F 4-Cl H 3-tetrahydrofuranyl 3-F 4-Cl H (R)-3-tetrahydrofuranyl 3-F4-Cl H (S)-3-tetrahydrofuranyl 3-F 4-Cl H Ph 3-F 4-Cl H 2-Cl-phenyl 3-F4-Cl H 3-Cl-phenyl 3-F 4-Cl H 4-Cl-phenyl 3-F 4-Cl H 2-pyridinyl 3-F4-Cl H 2-pyrimidinyl 3-F 4-Cl H 2-pyrazinyl 3-F 4-Cl H 2-thiazolyl 3-F4-Cl H 2-oxazolyl 3-F 4-Cl H 2-chloro-2-propenyl 3-F 4-Cl H3,3-dichloro-2-propenyl 3-F 4-Cl H CH₂-2-tetrahydrofuranyl 3-F 4-Cl HCH₂-2-tetrahydropyranyl 3-F 4-Cl H CH₂CH₂OH 3-F 4-Cl H CH₂OMe 3-F 4-Cl HCH₂CH₂OMe 3-F 4-Cl H CH₂CH₂CH₂OMe 3-Cl 5-CN H CH₂CH(Me)OMe 3-Cl 5-CN HCH(Me)OMe 3-Cl 5-CN H CH(Me)OEt 3-Cl 5-CN H CH(Me)CH₂OMe 3-Cl 5-CN HC(Me)₂CH₂OMe 3-Cl 5-CN H CH(Me)CH₂CH₂OMe 3-Cl 5-CN H (R)—CH(Me)CH₂OMe3-Cl 5-CN H (S)—CH(Me)CH₂OMe 3-Cl 5-CN H CH(Me)CH₂OH 3-Cl 5-CN HCH(Me)CH₂OC(═O)Me 3-Cl 5-CN H CH(Me)CH(OMe)₂ 3-Cl 5-CN HCH₂-2-dioxolanyl 3-Cl 5-CN H CH₂CH₂OCF₃ 3-Cl 5-CN H CH₂CH(Me)SMe 3-Cl5-CN H CH(Me)CH₂SMe 3-Cl 5-CN H CH₂CH₂S(═O)Me 3-Cl 5-CN H CH₂CH₂S(O)₂Me3-Cl 5-CN H CH₂CO₂Me 3-Cl 5-CN H CH(Me)CO₂Me 3-Cl 5-CN H CH₂C(═O)Me 3-Cl5-CN H CH₂CH₂C(═O)Me 3-Cl 5-CN H CH₂SiMe₃ 3-Cl 5-CN H CH₂CH₂SiMe₃ 3-Cl5-CN H CH₂-2-thienyl 3-Cl 5-CN H CH₂-2-pyridinyl 3-Cl 5-CN HCH₂-3-pyridinyl 3-Cl 5-CN H NH₂ 3-Cl 5-CN H NHCH₃ 3-Cl 5-CN H NHCH₂CF₃3-Cl 5-CN H NHCH₂CH₃ 3-Cl 5-CN H NHCH(Me)CH₃ 3-Cl 5-CN H NHCH₂CH(Me)₂3-Cl 5-CN H NHC(Me)₃ 3-Cl 5-CN H N(CH₃)₂ 3-Cl 5-CN H N(CH₃)CH₂CH₃ 3-Cl5-CN H N(CH₂CH₃)CH₂CH₃ 3-Cl 5-CN H CH₂CH₂CH₂OMe 3-F 4-Cl H CH₂CH(Me)OMe3-F 4-Cl H CH(Me)OMe 3-F 4-Cl H CH(Me)OEt 3-F 4-Cl H CH(Me)CH₂OMe 3-F4-Cl H C(Me)₂CH₂OMe 3-F 4-Cl H CH(Me)CH₂CH₂OMe 3-F 4-Cl H(R)—CH(Me)CH₂OMe 3-F 4-Cl H (S)—CH(Me)CH₂OMe 3-F 4-Cl H CH(Me)CH₂OH 3-F4-Cl H CH(Me)CH₂OC(═O)Me 3-F 4-Cl H CH(Me)CH(OMe)₂ 3-F 4-Cl HCH₂-2-dioxolanyl 3-F 4-Cl H CH₂CH₂OCF₃ 3-F 4-Cl H CH₂CH(Me)SMe 3-F 4-ClH CH(Me)CH₂SMe 3-F 4-Cl H CH₂CH₂S(═O)Me 3-F 4-Cl H CH₂CH₂S(O)₂Me 3-F4-Cl H CH₂CO₂Me 3-F 4-Cl H CH(Me)CO₂Me 3-F 4-Cl H CH₂C(═O)Me 3-F 4-Cl HCH₂CH₂C(═O)Me 3-F 4-Cl H CH₂SiMe₃ 3-F 4-Cl H CH₂CH₂SiMe₃ 3-F 4-Cl HCH₂-2-thienyl 3-F 4-Cl H CH₂-2-pyridinyl 3-F 4-Cl H CH₂-3-pyridinyl 3-F4-Cl H NH₂ 3-F 4-Cl H NHCH₃ 3-F 4-Cl H NHCH₂CF₃ 3-F 4-Cl H NHCH₂CH₃ 3-F4-Cl H NHCH(Me)CH₃ 3-F 4-Cl H NHCH₂CH(Me)₂ 3-F 4-Cl H NHC(Me)₃ 3-F 4-ClH N(CH₃)₂ 3-F 4-Cl H N(CH₃)CH₂CH₃ 3-F 4-Cl H N(CH₂CH₃)CH₂CH₃ 3-F 4-Cl HMe 3-F 4-CN H Et 3-F 4-CN H i-Pr 3-F 4-CN H n-Pr 3-F 4-CN H i-Bu 3-F4-CN H n-Bu 3-F 4-CN H s-Bu 3-F 4-CN H t-butyl 3-F 4-CN H n-Hex 3-F 4-CNH cyclopropyl 3-F 4-CN H cyclopentyl 3-F 4-CN H cyclohexyl 3-F 4-CN H2-cyclohexenyl 3-F 4-CN H 3-cyclohexenyl 3-F 4-CN H CH₂-c-Pr 3-F 4-CN H4-tetrahydropyranyl 3-F 4-CN H 3-tetrahydropyranyl 3-F 4-CN H(R)-3-tetrahydropyranyl 3-F 4-CN H (S)-3-tetrahydropyranyl 3-F 4-CN H3-tetrahydrofuranyl 3-F 4-CN H (R)-3-tetrahydrofuranyl 3-F 4-CN H(S)-3-tetrahydrofuranyl 3-F 4-CN H Ph 3-F 4-CN H 2-Cl-phenyl 3-F 4-CN H3-Cl-phenyl 3-F 4-CN H 4-Cl-phenyl 3-F 4-CN H 2-pyridinyl 3-F 4-CN H2-pyrimidinyl 3-F 4-CN H 2-pyrazinyl 3-F 4-CN H 2-thiazolyl 3-F 4-CN H2-oxazolyl 3-F 4-CN H 2-chloro-2-propenyl 3-F 4-CN H3,3-dichloro-2-propenyl 3-F 4-CN H CH₂-2-tetrahydrofuranyl 3-F 4-CN HCH₂-2-tetrahydropyranyl 3-F 4-CN H CH₂CH₂OH 3-F 4-CN H CH₂OMe 3-F 4-CN HMe 3-Cl 4-F H Et 3-Cl 4-F H i-Pr 3-Cl 4-F H n-Pr 3-Cl 4-F H i-Bu 3-Cl4-F H n-Bu 3-Cl 4-F H s-Bu 3-Cl 4-F H t-butyl 3-Cl 4-F H n-Hex 3-Cl 4-FH cyclopropyl 3-Cl 4-F H cyclopentyl 3-Cl 4-F H cyclohexyl 3-Cl 4-F H2-cyclohexenyl 3-Cl 4-F H 3-cyclohexenyl 3-Cl 4-F H CH₂-c-Pr 3-Cl 4-F H4-tetrahydropyranyl 3-Cl 4-F H 3-tetrahydropyranyl 3-Cl 4-F H(R)-3-tetrahydropyranyl 3-Cl 4-F H (S)-3-tetrahydropyranyl 3-Cl 4-F H3-tetrahydrofuranyl 3-Cl 4-F H (R)-3-tetrahydrofuranyl 3-Cl 4-F H(S)-3-tetrahydrofuranyl 3-Cl 4-F H Ph 3-Cl 4-F H 2-Cl-phenyl 3-Cl 4-F H3-Cl-phenyl 3-Cl 4-F H 4-Cl-phenyl 3-Cl 4-F H 2-pyridinyl 3-Cl 4-F H2-pyrimidinyl 3-Cl 4-F H 2-pyrazinyl 3-Cl 4-F H 2-thiazolyl 3-Cl 4-F H2-oxazolyl 3-Cl 4-F H 2-chloro-2-propenyl 3-Cl 4-F H3,3-dichloro-2-propenyl 3-Cl 4-F H CH₂-2-tetrahydrofuranyl 3-Cl 4-F HCH₂-2-tetrahydropyranyl 3-Cl 4-F H CH₂CH₂OH 3-Cl 4-F H CH₂OMe 3-Cl 4-F HCH₂CH₂OMe 3-F 4-CN H CH₂CH₂CH₂OMe 3-F 4-CN H CH₂CH(Me)OMe 3-F 4-CN HCH(Me)OMe 3-F 4-CN H CH(Me)OEt 3-F 4-CN H CH(Me)CH₂OMe 3-F 4-CN HC(Me)₂CH₂OMe 3-F 4-CN H CH(Me)CH₂CH₂OMe 3-F 4-CN H (R)—CH(Me)CH₂OMe 3-F4-CN H (S)—CH(Me)CH₂OMe 3-F 4-CN H CH(Me)CH₂OH 3-F 4-CN HCH(Me)CH₂OC(═O)Me 3-F 4-CN H CH(Me)CH(OMe)₂ 3-F 4-CN H CH₂-2-dioxolanyl3-F 4-CN H CH₂CH₂OCF₃ 3-F 4-CN H CH₂CH(Me)SMe 3-F 4-CN H CH(Me)CH₂SMe3-F 4-CN H CH₂CH₂S(═O)Me 3-F 4-CN H CH₂CH₂S(O)₂Me 3-F 4-CN H CH₂CO₂Me3-F 4-CN H CH(Me)CO₂Me 3-F 4-CN H CH₂C(═O)Me 3-F 4-CN H CH₂CH₂C(═O)Me3-F 4-CN H CH₂SiMe₃ 3-F 4-CN H CH₂CH₂SiMe₃ 3-F 4-CN H CH₂-2-thienyl 3-F4-CN H CH₂-2-pyridinyl 3-F 4-CN H CH₂-3-pyridinyl 3-F 4-CN H NH₂ 3-F4-CN H NHCH₃ 3-F 4-CN H NHCH₂CF₃ 3-F 4-CN H NHCH₂CH₃ 3-F 4-CN HNHCH(Me)CH₃ 3-F 4-CN H NHCH₂CH(Me)₂ 3-F 4-CN H NHC(Me)₃ 3-F 4-CN HN(CH₃)₂ 3-F 4-CN H N(CH₃)CH₂CH₃ 3-F 4-CN H CH₂CH₂OMe 3-Cl 4-F HCH₂CH₂CH₂OMe 3-Cl 4-F H CH₂CH(Me)OMe 3-Cl 4-F H CH(Me)OMe 3-Cl 4-F HCH(Me)OEt 3-Cl 4-F H CH(Me)CH₂OMe 3-Cl 4-F H C(Me)₂CH₂OMe 3-Cl 4-F HCH(Me)CH₂CH₂OMe 3-Cl 4-F H (R)—CH(Me)CH₂OMe 3-Cl 4-F H (S)—CH(Me)CH₂OMe3-Cl 4-F H CH(Me)CH₂OH 3-Cl 4-F H CH(Me)CH₂OC(═O)Me 3-Cl 4-F HCH(Me)CH(OMe)₂ 3-Cl 4-F H CH₂-2-dioxolanyl 3-Cl 4-F H CH₂CH₂OCF₃ 3-Cl4-F H CH₂CH(Me)SMe 3-Cl 4-F H CH(Me)CH₂SMe 3-Cl 4-F H CH₂CH₂S(═O)Me 3-Cl4-F H CH₂CH₂S(O)₂Me 3-Cl 4-F H CH₂CO₂Me 3-Cl 4-F H CH(Me)CO₂Me 3-Cl 4-FH CH₂C(═O)Me 3-Cl 4-F H CH₂CH₂C(═O)Me 3-Cl 4-F H CH₂SiMe₃ 3-Cl 4-F HCH₂CH₂SiMe₃ 3-Cl 4-F H CH₂-2-thienyl 3-Cl 4-F H CH₂-2-pyridinyl 3-Cl 4-FH CH₂-3-pyridinyl 3-Cl 4-F H NH₂ 3-Cl 4-F H NHCH₃ 3-Cl 4-F H NHCH₂CF₃3-Cl 4-F H NHCH₂CH₃ 3-Cl 4-F H NHCH(Me)CH₃ 3-Cl 4-F H NHCH₂CH(Me)₂ 3-Cl4-F H NHC(Me)₃ 3-Cl 4-F H N(CH₃)₂ 3-Cl 4-F H N(CH₃)CH₂CH₃ 3-Cl 4-F HN(CH₂CH₃)CH₂CH₃ 3-F 4-CN H Me H 4-F H Et H 4-F H i-Pr H 4-F H n-Pr H 4-FH i-Bu H 4-F H n-Bu H 4-F H s-Bu H 4-F H t-butyl H 4-F H n-Hex H 4-F Hcyclopropyl H 4-F H cyclopentyl H 4-F H cyclohexyl H 4-F H2-cyclohexenyl H 4-F H 3-cyclohexenyl H 4-F H CH₂-c-Pr H 4-F H4-tetrahydropyranyl H 4-F H 3-tetrahydropyranyl H 4-F H(R)-3-tetrahydropyranyl H 4-F H (S)-3-tetrahydropyranyl H 4-F H3-tetrahydrofuranyl H 4-F H (R)-3-tetrahydrofuranyl H 4-F H(S)-3-tetrahydrofuranyl H 4-F H Ph H 4-F H 2-Cl-phenyl H 4-F H3-Cl-phenyl H 4-F H 4-Cl-phenyl H 4-F H 2-pyridinyl H 4-F H2-pyrimidinyl H 4-F H 2-pyrazinyl H 4-F H 2-thiazolyl H 4-F H 2-oxazolylH 4-F H 2-chloro-2-propenyl H 4-F H 3,3-dichloro-2-propenyl H 4-F HCH₂-2-tetrahydrofuranyl H 4-F H CH₂-2-tetrahydropyranyl H 4-F H CH₂CH₂OHH 4-F H N(CH₂CH₃)CH₂CH₃ 3-Cl 4-F H Me H 2-F H Et H 2-F H i-Pr H 2-F Hn-Pr H 2-F H i-Bu H 2-F H n-Bu H 2-F H s-Bu H 2-F H t-butyl H 2-F Hn-Hex H 2-F H cyclopropyl H 2-F H cyclopentyl H 2-F H cyclohexyl H 2-F H2-cyclohexenyl H 2-F H 3-cyclohexenyl H 2-F H CH₂-c-Pr H 2-F H4-tetrahydropyranyl H 2-F H 3-tetrahydropyranyl H 2-F H(R)-3-tetrahydropyranyl H 2-F H (S)-3-tetrahydropyranyl H 2-F H3-tetrahydrofuranyl H 2-F H (R)-3-tetrahydrofuranyl H 2-F H(S)-3-tetrahydrofuranyl H 2-F H Ph H 2-F H 2-Cl-phenyl H 2-F H3-Cl-phenyl H 2-F H 4-Cl-phenyl H 2-F H 2-pyridinyl H 2-F H2-pyrimidinyl H 2-F H 2-pyrazinyl H 2-F H 2-thiazolyl H 2-F H 2-oxazolylH 2-F H 2-chloro-2-propenyl H 2-F H 3,3-dichloro-2-propenyl H 2-F HCH₂-2-tetrahydrofuranyl H 2-F H CH₂-2-tetrahydropyranyl H 2-F H CH₂CH₂OHH 2-F H CH₂OMe H 4-F H CH₂CH₂OMe H 4-F H CH₂CH₂CH₂OMe H 4-F HCH₂CH(Me)OMe H 4-F H CH(Me)OMe H 4-F H CH(Me)OEt H 4-F H CH(Me)CH₂OMe H4-F H C(Me)₂CH₂OMe H 4-F H CH(Me)CH₂CH₂OMe H 4-F H (R)—CH(Me)CH₂OMe H4-F H (S)—CH(Me)CH₂OMe H 4-F H CH(Me)CH₂OH H 4-F H CH(Me)CH₂OC(═O)Me H4-F H CH(Me)CH(OMe)₂ H 4-F H CH₂-2-dioxolanyl H 4-F H CH₂CH₂OCF₃ H 4-F HCH₂CH(Me)SMe H 4-F H CH(Me)CH₂SMe H 4-F H CH₂CH₂S(═O)Me H 4-F HCH₂CH₂S(O)₂Me H 4-F H CH₂CO₂Me H 4-F H CH(Me)CO₂Me H 4-F H CH₂C(═O)Me H4-F H CH₂CH₂C(═O)Me H 4-F H CH₂SiMe₃ H 4-F H CH₂CH₂SiMe₃ H 4-F HCH₂-2-thienyl H 4-F H CH₂-2-pyridinyl H 4-F H CH₂-3-pyridinyl H 4-F HNH₂ H 4-F H NHCH₃ H 4-F H NHCH₂CF₃ H 4-F H NHCH₂CH₃ H 4-F H NHCH(Me)CH₃H 4-F H NHCH₂CH(Me)₂ H 4-F H NHC(Me)₃ H 4-F H N(CH₃)₂ H 4-F H CH₂OMe H2-F H CH₂CH₂OMe H 2-F H CH₂CH₂CH₂OMe H 2-F H CH₂CH(Me)OMe H 2-F HCH(Me)OMe H 2-F H CH(Me)OEt H 2-F H CH(Me)CH₂OMe H 2-F H C(Me)₂CH₂OMe H2-F H CH(Me)CH₂CH₂OMe H 2-F H (R)—CH(Me)CH₂OMe H 2-F H (S)—CH(Me)CH₂OMeH 2-F H CH(Me)CH₂OH H 2-F H CH(Me)CH₂OC(═O)Me H 2-F H CH(Me)CH(OMe)₂ H2-F H CH₂-2-dioxolanyl H 2-F H CH₂CH₂OCF₃ H 2-F H CH₂CH(Me)SMe H 2-F HCH(Me)CH₂SMe H 2-F H CH₂CH₂S(═O)Me H 2-F H CH₂CH₂S(O)₂Me H 2-F HCH₂CO₂Me H 2-F H CH(Me)CO₂Me H 2-F H CH₂C(═O)Me H 2-F H CH₂CH₂C(═O)Me H2-F H CH₂SiMe₃ H 2-F H CH₂CH₂SiMe₃ H 2-F H CH₂-2-thienyl H 2-F HCH₂-2-pyridinyl H 2-F H CH₂-3-pyridinyl H 2-F H NH₂ H 2-F H NHCH₃ H 2-FH NHCH₂CF₃ H 2-F H NHCH₂CH₃ H 2-F H NHCH(Me)CH₃ H 2-F H NHCH₂CH(Me)₂ H2-F H NHC(Me)₃ H 2-F H N(CH₃)₂ H 2-F H N(CH₃)CH₂CH₃ H 4-F HN(CH₂CH₃)CH₂CH₃ H 4-F H Me 3-F 5-NO₂ H Et 3-F 5-NO₂ H i-Pr 3-F 5-NO₂ Hn-Pr 3-F 5-NO₂ H i-Bu 3-F 5-NO₂ H n-Bu 3-F 5-NO₂ H s-Bu 3-F 5-NO₂ Ht-butyl 3-F 5-NO₂ H n-Hex 3-F 5-NO₂ H cyclopropyl 3-F 5-NO₂ Hcyclopentyl 3-F 5-NO₂ H cyclohexyl 3-F 5-NO₂ H 2-cyclohexenyl 3-F 5-NO₂H 3-cyclohexenyl 3-F 5-NO₂ H CH₂-c-Pr 3-F 5-NO₂ H 4-tetrahydropyranyl3-F 5-NO₂ H 3-tetrahydropyranyl 3-F 5-NO₂ H (R)-3-tetrahydropyranyl 3-F5-NO₂ H (S)-3-tetrahydropyranyl 3-F 5-NO₂ H 3-tetrahydrofuranyl 3-F5-NO₂ H (R)-3-tetrahydrofuranyl 3-F 5-NO₂ H (S)-3-tetrahydrofuranyl 3-F5-NO₂ H Ph 3-F 5-NO₂ H 2-Cl-phenyl 3-F 5-NO₂ H 3-Cl-phenyl 3-F 5-NO₂ H4-Cl-phenyl 3-F 5-NO₂ H 2-pyridinyl 3-F 5-NO₂ H 2-pyrimidinyl 3-F 5-NO₂H 2-pyrazinyl 3-F 5-NO₂ H 2-thiazolyl 3-F 5-NO₂ H 2-oxazolyl 3-F 5-NO₂ H2-chloro-2-propenyl 3-F 5-NO₂ H 3,3-dichloro-2-propenyl 3-F 5-NO₂ HCH₂-2-tetrahydrofuranyl 3-F 5-NO₂ H CH₂-2-tetrahydropyranyl 3-F 5-NO₂ HN(CH₃)CH₂CH₃ H 2-F H N(CH₂CH₃)CH₂CH₃ H 2-F H Me 3-F 4-F 5-F Et 3-F 4-F5-F i-Pr 3-F 4-F 5-F n-Pr 3-F 4-F 5-F i-Bu 3-F 4-F 5-F n-Bu 3-F 4-F 5-Fs-Bu 3-F 4-F 5-F t-butyl 3-F 4-F 5-F n-Hex 3-F 4-F 5-F cyclopropyl 3-F4-F 5-F cyclopentyl 3-F 4-F 5-F cyclohexyl 3-F 4-F 5-F 2-cyclohexenyl3-F 4-F 5-F 3-cyclohexenyl 3-F 4-F 5-F CH₂-c-Pr 3-F 4-F 5-F4-tetrahydropyranyl 3-F 4-F 5-F 3-tetrahydropyranyl 3-F 4-F 5-F(R)-3-tetrahydropyranyl 3-F 4-F 5-F (S)-3-tetrahydropyranyl 3-F 4-F 5-F3-tetrahydrofuranyl 3-F 4-F 5-F (R)-3-tetrahydrofuranyl 3-F 4-F 5-F(S)-3-tetrahydrofuranyl 3-F 4-F 5-F Ph 3-F 4-F 5-F 2-Cl-phenyl 3-F 4-F5-F 3-Cl-phenyl 3-F 4-F 5-F 4-Cl-phenyl 3-F 4-F 5-F 2-pyridinyl 3-F 4-F5-F 2-pyrimidinyl 3-F 4-F 5-F 2-pyrazinyl 3-F 4-F 5-F 2-thiazolyl 3-F4-F 5-F 2-oxazolyl 3-F 4-F 5-F 2-chloro-2-propenyl 3-F 4-F 5-F3,3-dichloro-2-propenyl 3-F 4-F 5-F CH₂-2-tetrahydrofuranyl 3-F 4-F 5-FCH₂-2-tetrahydropyranyl 3-F 4-F 5-F CH₂CH₂OH 3-F 5-NO₂ H CH₂OMe 3-F5-NO₂ H CH₂CH₂OMe 3-F 5-NO₂ H CH₂CH₂CH₂OMe 3-F 5-NO₂ H CH₂CH(Me)OMe 3-F5-NO₂ H CH(Me)OMe 3-F 5-NO₂ H CH(Me)OEt 3-F 5-NO₂ H CH(Me)CH₂OMe 3-F5-NO₂ H C(Me)₂CH₂OMe 3-F 5-NO₂ H CH(Me)CH₂CH₂OMe 3-F 5-NO₂ H(R)—CH(Me)CH₂OMe 3-F 5-NO₂ H (S)—CH(Me)CH₂OMe 3-F 5-NO₂ H CH(Me)CH₂OH3-F 5-NO₂ H CH(Me)CH₂OC(═O)Me 3-F 5-NO₂ H CH(Me)CH(OMe)₂ 3-F 5-NO₂ HCH₂-2-dioxolanyl 3-F 5-NO₂ H CH₂CH₂OCF₃ 3-F 5-NO₂ H CH₂CH(Me)SMe 3-F5-NO₂ H CH(Me)CH₂SMe 3-F 5-NO₂ H CH₂CH₂S(═O)Me 3-F 5-NO₂ H CH₂CH₂S(O)₂Me3-F 5-NO₂ H CH₂CO₂Me 3-F 5-NO₂ H CH(Me)CO₂Me 3-F 5-NO₂ H CH₂C(═O)Me 3-F5-NO₂ H CH₂CH₂C(═O)Me 3-F 5-NO₂ H CH₂SiMe₃ 3-F 5-NO₂ H CH₂CH₂SiMe₃ 3-F5-NO₂ H CH₂-2-thienyl 3-F 5-NO₂ H CH₂-2-pyridinyl 3-F 5-NO₂ HCH₂-3-pyridinyl 3-F 5-NO₂ H NH₂ 3-F 5-NO₂ H NHCH₃ 3-F 5-NO₂ H NHCH₂CF₃3-F 5-NO₂ H NHCH₂CH₃ 3-F 5-NO₂ H NHCH(Me)CH₃ 3-F 5-NO₂ H NHCH₂CH(Me)₂3-F 5-NO₂ H NHC(Me)₃ 3-F 5-NO₂ H CH₂CH₂OH 3-F 4-F 5-F CH₂OMe 3-F 4-F 5-FCH₂CH₂OMe 3-F 4-F 5-F CH₂CH₂CH₂OMe 3-F 4-F 5-F CH₂CH(Me)OMe 3-F 4-F 5-FCH(Me)OMe 3-F 4-F 5-F CH(Me)OEt 3-F 4-F 5-F CH(Me)CH₂OMe 3-F 4-F 5-FC(Me)₂CH₂OMe 3-F 4-F 5-F CH(Me)CH₂CH₂OMe 3-F 4-F 5-F (R)—CH(Me)CH₂OMe3-F 4-F 5-F (S)—CH(Me)CH₂OMe 3-F 4-F 5-F CH(Me)CH₂OH 3-F 4-F 5-FCH(Me)CH₂OC(═O)Me 3-F 4-F 5-F CH(Me)CH(OMe)₂ 3-F 4-F 5-FCH₂-2-dioxolanyl 3-F 4-F 5-F CH₂CH₂OCF₃ 3-F 4-F 5-F CH₂CH(Me)SMe 3-F 4-F5-F CH(Me)CH₂SMe 3-F 4-F 5-F CH₂CH₂S(═O)Me 3-F 4-F 5-F CH₂CH₂S(O)₂Me 3-F4-F 5-F CH₂CO₂Me 3-F 4-F 5-F CH(Me)CO₂Me 3-F 4-F 5-F CH₂C(═O)Me 3-F 4-F5-F CH₂CH₂C(═O)Me 3-F 4-F 5-F CH₂SiMe₃ 3-F 4-F 5-F CH₂CH₂SiMe₃ 3-F 4-F5-F CH₂-2-thienyl 3-F 4-F 5-F CH₂-2-pyridinyl 3-F 4-F 5-FCH₂-3-pyridinyl 3-F 4-F 5-F NH₂ 3-F 4-F 5-F NHCH₃ 3-F 4-F 5-F NHCH₂CF₃3-F 4-F 5-F NHCH₂CH₃ 3-F 4-F 5-F NHCH(Me)CH₃ 3-F 4-F 5-F NHCH₂CH(Me)₂3-F 4-F 5-F NHC(Me)₃ 3-F 4-F 5-F N(CH₃)₂ 3-F 5-NO₂ H N(CH₃)CH₂CH₃ 3-F5-NO₂ H N(CH₂CH₃)CH₂CH₃ 3-F 5-NO₂ H Me 3-F 4-Me 5-F Et 3-F 4-Me 5-F i-Pr3-F 4-Me 5-F n-Pr 3-F 4-Me 5-F i-Bu 3-F 4-Me 5-F n-Bu 3-F 4-Me 5-F s-Bu3-F 4-Me 5-F t-butyl 3-F 4-Me 5-F n-Hex 3-F 4-Me 5-F cyclopropyl 3-F4-Me 5-F cyclopentyl 3-F 4-Me 5-F cyclohexyl 3-F 4-Me 5-F 2-cyclohexenyl3-F 4-Me 5-F 3-cyclohexenyl 3-F 4-Me 5-F CH₂-c-Pr 3-F 4-Me 5-F4-tetrahydropyranyl 3-F 4-Me 5-F 3-tetrahydropyranyl 3-F 4-Me 5-F(R)-3-tetrahydropyranyl 3-F 4-Me 5-F (S)-3-tetrahydropyranyl 3-F 4-Me5-F 3-tetrahydrofuranyl 3-F 4-Me 5-F (R)-3-tetrahydrofuranyl 3-F 4-Me5-F (S)-3-tetrahydrofuranyl 3-F 4-Me 5-F Ph 3-F 4-Me 5-F 2-Cl-phenyl 3-F4-Me 5-F 3-Cl-phenyl 3-F 4-Me 5-F 4-Cl-phenyl 3-F 4-Me 5-F 2-pyridinyl3-F 4-Me 5-F 2-pyrimidinyl 3-F 4-Me 5-F 2-pyrazinyl 3-F 4-Me 5-F2-thiazolyl 3-F 4-Me 5-F 2-oxazolyl 3-F 4-Me 5-F 2-chloro-2-propenyl 3-F4-Me 5-F 3,3-dichloro-2-propenyl 3-F 4-Me 5-F CH₂-2-tetrahydrofuranyl3-F 4-Me 5-F N(CH₃)₂ 3-F 4-F 5-F N(CH₃)CH₂CH₃ 3-F 4-F 5-FN(CH₂CH₃)CH₂CH₃ 3-F 4-F 5-F Me H H H Et H H H i-Pr H H H n-Pr H H H i-BuH H H n-Bu H H H s-Bu H H H t-butyl H H H n-Hex H H H cyclopropyl H H Hcyclopentyl H H H cyclohexyl H H H 2-cyclohexenyl H H H 3-cyclohexenyl HH H CH₂-c-Pr H H H 4-tetrahydropyranyl H H H 3-tetrahydropyranyl H H H(R)-3-tetrahydropyranyl H H H (S)-3-tetrahydropyranyl H H H3-tetrahydrofuranyl H H H (R)-3-tetrahydrofuranyl H H H(S)-3-tetrahydrofuranyl H H H Ph H H H 2-Cl-phenyl H H H 3-Cl-phenyl H HH 4-Cl-phenyl H H H 2-pyridinyl H H H 2-pyrimidinyl H H H 2-pyrazinyl HH H 2-thiazolyl H H H 2-oxazolyl H H H 2-chloro-2-propenyl H H H3,3-dichloro-2-propenyl H H H CH₂-2-tetrahydrofuranyl H H HCH₂-2-tetrahydropyranyl 3-F 4-Me 5-F CH₂CH₂OH 3-F 4-Me 5-F CH₂OMe 3-F4-Me 5-F CH₂CH₂OMe 3-F 4-Me 5-F CH₂CH₂CH₂OMe 3-F 4-Me 5-F CH₂CH(Me)OMe3-F 4-Me 5-F CH(Me)OMe 3-F 4-Me 5-F CH(Me)OEt 3-F 4-Me 5-F CH(Me)CH₂OMe3-F 4-Me 5-F C(Me)₂CH₂OMe 3-F 4-Me 5-F CH(Me)CH₂CH₂OMe 3-F 4-Me 5-F(R)—CH(Me)CH₂OMe 3-F 4-Me 5-F (S)—CH(Me)CH₂OMe 3-F 4-Me 5-F CH(Me)CH₂OH3-F 4-Me 5-F CH(Me)CH₂OC(═O)Me 3-F 4-Me 5-F CH(Me)CH(OMe)₂ 3-F 4-Me 5-FCH₂-2-dioxolanyl 3-F 4-Me 5-F CH₂CH₂OCF₃ 3-F 4-Me 5-F CH₂CH(Me)SMe 3-F4-Me 5-F CH(Me)CH₂SMe 3-F 4-Me 5-F CH₂CH₂S(═O)Me 3-F 4-Me 5-FCH₂CH₂S(O)₂Me 3-F 4-Me 5-F CH₂CO₂Me 3-F 4-Me 5-F CH(Me)CO₂Me 3-F 4-Me5-F CH₂C(═O)Me 3-F 4-Me 5-F CH₂CH₂C(═O)Me 3-F 4-Me 5-F CH₂SiMe₃ 3-F 4-Me5-F CH₂CH₂SiMe₃ 3-F 4-Me 5-F CH₂-2-thienyl 3-F 4-Me 5-F CH₂-2-pyridinyl3-F 4-Me 5-F CH₂-3-pyridinyl 3-F 4-Me 5-F NH₂ 3-F 4-Me 5-F NHCH₃ 3-F4-Me 5-F NHCH₂CF₃ 3-F 4-Me 5-F NHCH₂CH₃ 3-F 4-Me 5-F NHCH(Me)CH₃ 3-F4-Me 5-F NHCH₂CH(Me)₂ 3-F 4-Me 5-F CH₂-2-tetrahydropyranyl H H HCH₂CH₂OH H H H CH₂OMe H H H CH₂CH₂OMe H H H CH₂CH₂CH₂OMe H H HCH₂CH(Me)OMe H H H CH(Me)OMe H H H CH(Me)OEt H H H CH(Me)CH₂OMe H H HC(Me)₂CH₂OMe H H H CH(Me)CH₂CH₂OMe H H H (R)—CH(Me)CH₂OMe H H H(S)—CH(Me)CH₂OMe H H H CH(Me)CH₂OH H H H CH(Me)CH₂OC(═O)Me H H HCH(Me)CH(OMe)₂ H H H CH₂-2-dioxolanyl H H H CH₂CH₂OCF₃ H H HCH₂CH(Me)SMe H H H CH(Me)CH₂SMe H H H CH₂CH₂S(═O)Me H H H CH₂CH₂S(O)₂MeH H H CH₂CO₂Me H H H CH(Me)CO₂Me H H H CH₂C(═O)Me H H H CH₂CH₂C(═O)Me HH H CH₂SiMe₃ H H H CH₂CH₂SiMe₃ H H H CH₂-2-thienyl H H H CH₂-2-pyridinylH H H CH₂-3-pyridinyl H H H NH₂ H H H NHCH₃ H H H NHCH₂CF₃ H H HNHCH₂CH₃ H H H NHCH(Me)CH₃ H H H NHCH₂CH(Me)₂ H H H NHC(Me)₃ 3-F 4-Me5-F N(CH₃)₂ 3-F 4-Me 5-F N(CH₃)CH₂CH₃ 3-F 4-Me 5-F N(CH2CH₃)CH₂CH₃ 3-F4-Me 5-F NHC(Me)₃ H H H N(CH₃)₂ H H H N(CH₃)CH₂CH₃ H H H N(CH₂CH₃)CH₂CH₃H H H

TABLE 2

R¹ R^(7a) R^(7b) R¹ R^(7a) R^(7b) t-butyl H 6-F t-butyl H 6-Clcyclopropyl H 6-F cyclopropyl H 6-Cl cyclohexyl H 6-F cyclohexyl H 6-ClCH-c-Pr H 6-F CH-c-Pr H 6-Cl 4-tetrahydropyranyl H 6-F4-tetrahydropyranyl H 6-Cl 3-tetrahydropyranyl H 6-F 3-tetrahydropyranylH 6-Cl (R)-3-tetrahydropyranyl H 6-F (R)-3-tetrahydropyranyl H 6-Cl(S)-3-tetrahydropyranyl H 6-F (S)-3-tetrahydropyranyl H 6-Cl3-tetrahydrofuranyl H 6-F 3-tetrahydrofuranyl H 6-Cl(R)-3-tetrahydrofuranyl H 6-F (R)-3-tetrahydrofuranyl H 6-Cl(S)-3-tetrahydrofuranyl H 6-F (S)-3-tetrahydrofuranyl H 6-Cl 2-pyridinylH 6-F 2-pyridinyl H 6-Cl CH₂-2-tetrahydrofuranyl H 6-FCH₂-2-tetrahydrofuranyl H 6-Cl CH₂-2-tetrahydropyranyl H 6-FCH₂-2-tetrahydropyranyl H 6-Cl CH₂OMe H 6-F CH₂OMe H 6-Cl CH₂CH₂OMe H6-F CH₂CH₂OMe H 6-Cl CH₂CH₂CH₂OMe H 6-F CH₂CH₂CH₂OMe H 6-Cl CH₂CH(Me)OMeH 6-F CH₂CH(Me)OMe H 6-Cl CH(Me)OMe H 6-F CH(Me)OMe H 6-Cl CH(Me)OEt H6-F CH(Me)OEt H 6-Cl CH(Me)CH₂OMe H 6-F CH(Me)CH₂OMe H 6-Cl C(Me)₂CH₂OMeH 6-F C(Me)₂CH₂OMe H 6-Cl CH(Me)CH₂CH₂OMe H 6-F CH(Me)CH₂CH₂OMe H 6-Cl(R)—CH(Me)CH₂OMe H 6-F (R)—CH(Me)CH₂OMe H 6-Cl (S)-CH(Me)CH₂OMe H 6-F(S)-CH(Me)CH₂OMe H 6-Cl CH(Me)CH₂OH H 6-F CH(Me)CH₂OH H 6-ClCH(Me)CH₂OC(═O)Me H 6-F CH(Me)CH₂OC(═O)Me H 6-Cl CH₂CH₂OCF₃ H 6-FCH₂CH₂OCF₃ H 6-Cl NH₂ H 6-F NH₂ H 6-Cl NHCH₃ H 6-F NHCH₃ H 6-Cl NHCH₂CF₃H 6-F NHCH₂CF₃ H 6-Cl NHCH₂CH₃ H 6-F NHCH₂CH₃ H 6-Cl NHCH(Me)CH₃ H 6-FNHCH(Me)CH₃ H 6-Cl NHC(Me)₃ H 6-F NHC(Me)₃ H 6-Cl N(CH₃)₂ H 6-F N(CH₃)₂H 6-Cl t-butyl H 5-F t-butyl H 6-CN cyclopropyl H 5-F cyclopropyl H 6-CNcyclohexyl H 5-F cyclohexyl H 6-CN CH-c-Pr H 5-F CH-c-Pr H 6-CN4-tetrahydropyranyl H 5-F 4-tetrahydropyranyl H 6-CN 3-tetrahydropyranylH 5-F 3-tetrahydropyranyl H 6-CN (R)-3-tetrahydropyranyl H 5-F(R)-3-tetrahydropyranyl H 6-CN (S)-3-tetrahydropyranyl H 5-F(S)-3-tetrahydropyranyl H 6-CN 3-tetrahydrofuranyl H 5-F3-tetrahydrofuranyl H 6-CN (R)-3-tetrahydrofuranyl H 5-F(R)-3-tetrahydrofuranyl H 6-CN (S)-3-tetrahydrofuranyl H 5-F(S)-3-tetrahydrofuranyl H 6-CN 2-pyridinyl H 5-F 2-pyridinyl H 6-CNCH₂-2-tetrahydrofuranyl H 5-F CH₂-2-tetrahydrofuranyl H 6-CNCH₂-2-tetrahydropyranyl H 5-F CH₂-2-tetrahydropyranyl H 6-CN CH₂OMe H5-F CH₂OMe H 6-CN CH₂CH₂OMe H 5-F CH₂CH₂OMe H 6-CN CH₂CH₂CH₂OMe H 5-FCH₂CH₂CH₂OMe H 6-CN CH₂CH(Me)OMe H 5-F CH₂CH(Me)OMe H 6-CN CH(Me)OMe H5-F CH(Me)OMe H 6-CN CH(Me)OEt H 5-F CH(Me)OEt H 6-CN CH(Me)CH₂OMe H 5-FCH(Me)CH₂OMe H 6-CN C(Me)₂CH₂OMe H 5-F C(Me)₂CH₂OMe H 6-CNCH(Me)CH₂CH₂OMe H 5-F CH(Me)CH₂CH₂OMe H 6-CN (R)—CH(Me)CH₂OMe H 5-F(R)—CH(Me)CH₂OMe H 6-CN (S)-CH(Me)CH₂OMe H 5-F (S)-CH(Me)CH₂OMe H 6-CNCH(Me)CH₂OH H 5-F CH(Me)CH₂OH H 6-CN CH(Me)CH₂OC(═O)Me H 5-FCH(Me)CH₂OC(═O)Me H 6-CN CH₂CH₂OCF₃ H 5-F CH₂CH₂OCF₃ H 6-CN NH₂ H 5-FNH₂ H 6-CN NHCH₃ H 5-F NHCH₃ H 6-CN NHCH₂CF₃ H 5-F NHCH₂CF₃ H 6-CNNHCH₂CH₃ H 5-F NHCH₂CH₃ H 6-CN NHCH(Me)CH₃ H 5-F NHCH(Me)CH₃ H 6-CNNHC(Me)₃ H 5-F NHC(Me)₃ H 6-CN N(CH₃)₂ H 5-F N(CH₃)₂ H 6-CN t-butyl 5-F6-CN t-butyl H H cyclopropyl 5-F 6-CN cyclopropyl H H cyclohexyl 5-F6-CN cyclohexyl H H CH-c-Pr 5-F 6-CN CH-c-Pr H H 4-tetrahydropyranyl 5-F6-CN 4-tetrahydropyranyl H H 3-tetrahydropyranyl 5-F 6-CN3-tetrahydropyranyl H H (R)-3-tetrahydropyranyl 5-F 6-CN(R)-3-tetrahydropyranyl H H (S)-3-tetrahydropyranyl 5-F 6-CN(S)-3-tetrahydropyranyl H H 3-tetrahydrofuranyl 5-F 6-CN3-tetrahydrofuranyl H H (R)-3-tetrahydrofuranyl 5-F 6-CN(R)-3-tetrahydrofuranyl H H (S)-3-tetrahydrofuranyl 5-F 6-CN(S)-3-tetrahydrofuranyl H H 2-pyridinyl 5-F 6-CN 2-pyridinyl H HCH₂-2-tetrahydrofuranyl 5-F 6-CN CH₂-2-tetrahydrofuranyl H HCH₂-2-tetrahydropyranyl 5-F 6-CN CH₂-2-tetrahydropyranyl H H CH₂OMe 5-F6-CN CH₂OMe H H CH₂CH₂OMe 5-F 6-CN CH₂CH₂OMe H H CH₂CH₂CH₂OMe 5-F 6-CNCH₂CH₂CH₂OMe H H CH₂CH(Me)OMe 5-F 6-CN CH₂CH(Me)OMe H H CH(Me)OMe 5-F6-CN CH(Me)OMe H H CH(Me)OEt 5-F 6-CN CH(Me)OEt H H CH(Me)CH₂OMe 5-F6-CN CH(Me)CH₂OMe H H C(Me)₂CH₂OMe 5-F 6-CN C(Me)₂CH₂OMe H HCH(Me)CH₂CH₂OMe 5-F 6-CN CH(Me)CH₂CH₂OMe H H (R)—CH(Me)CH₂OMe 5-F 6-CN(R)—CH(Me)CH₂OMe H H (S)-CH(Me)CH₂OMe 5-F 6-CN (S)-CH(Me)CH₂OMe H HCH(Me)CH₂OH 5-F 6-CN CH(Me)CH₂OH H H CH(Me)CH₂OC(═O)Me 5-F 6-CNCH(Me)CH₂OC(═O)Me H H CH₂CH₂OCF₃ 5-F 6-CN CH₂CH₂OCF₃ H H NH₂ 5-F 6-CNNH₂ H H NHCH₃ 5-F 6-CN NHCH₃ H H NHCH₂CF₃ 5-F 6-CN NHCH₂CF₃ H H NHCH₂CH₃5-F 6-CN NHCH₂CH₃ H H NHCH(Me)CH₃ 5-F 6-CN NHCH(Me)CH₃ H H NHC(Me)₃ 5-F6-CN NHC(Me)₃ H H N(CH₃)₂ 5-F 6-CN N(CH₃)₂ H H

TABLE 3

R¹ R^(7a) R^(7b) R¹ R^(7a) R^(7b) t-butyl 2-F H t-butyl 2-CN Hcyclopropyl 2-F H cyclopropyl 2-CN H cyclohexyl 2-F H cyclohexyl 2-CN HCH-c-Pr 2-F H CH-c-Pr 2-CN H 4-tetrahydropyranyl 2-F H4-tetrahydropyranyl 2-CN H 3-tetrahydropyranyl 2-F H 3-tetrahydropyranyl2-CN H (R)-3-tetrahydropyranyl 2-F H (R)-3-tetrahydropyranyl 2-CN H(S)-3-tetrahydropyranyl 2-F H (S)-3-tetrahydropyranyl 2-CN H3-tetrahydrofuranyl 2-F H 3-tetrahydrofuranyl 2-CN H(R)-3-tetrahydrofuranyl 2-F H (R)-3-tetrahydrofuranyl 2-CN H(S)-3-tetrahydrofuranyl 2-F H (S)-3-tetrahydrofuranyl 2-CN H 2-pyridinyl2-F H 2-pyridinyl 2-CN H CH₂-2-tetrahydrofuranyl 2-F HCH₂-2-tetrahydrofuranyl 2-CN H CH₂-2-tetrahydropyranyl 2-F HCH₂-2-tetrahydropyranyl 2-CN H CH₂OMe 2-F H CH₂OMe 2-CN H CH₂CH₂OMe 2-FH CH₂CH₂OMe 2-CN H CH₂CH₂CH₂OMe 2-F H CH₂CH₂CH₂OMe 2-CN H CH₂CH(Me)OMe2-F H CH₂CH(Me)OMe 2-CN H CH(Me)OMe 2-F H CH(Me)OMe 2-CN H CH(Me)OEt 2-FH CH(Me)OEt 2-CN H CH(Me)CH₂OMe 2-F H CH(Me)CH₂OMe 2-CN H C(Me)₂CH₂OMe2-F H C(Me)₂CH₂OMe 2-CN H CH(Me)CH₂CH₂OMe 2-F H CH(Me)CH₂CH₂OMe 2-CN H(R)—CH(Me)CH₂OMe 2-F H (R)—CH(Me)CH₂OMe 2-CN H (S)-CH(Me)CH₂OMe 2-F H(S)-CH(Me)CH₂OMe 2-CN H CH(Me)CH₂OH 2-F H CH(Me)CH₂OH 2-CN HCH(Me)CH₂OC(═O)Me 2-F H CH(Me)CH₂OC(═O)Me 2-CN H CH₂CH₂OCF₃ 2-F HCH₂CH₂OCF₃ 2-CN H NH₂ 2-F H NH₂ 2-CN H NHCH₃ 2-F H NHCH₃ 2-CN H NHCH₂CF₃2-F H NHCH₂CF₃ 2-CN H NHCH₂CH₃ 2-F H NHCH₂CH₃ 2-CN H NHCH(Me)CH₃ 2-F HNHCH(Me)CH₃ 2-CN H NHC(Me)₃ 2-F H NHC(Me)₃ 2-CN H N(CH₃)₂ 2-F H N(CH₃)₂2-CN H t-butyl 2-CN 6-Cl t-butyl H H cyclopropyl 2-CN 6-Cl cyclopropyl HH cyclohexyl 2-CN 6-Cl cyclohexyl H H CH-c-Pr 2-CN 6-Cl CH-c-Pr H H4-tetrahydropyranyl 2-CN 6-Cl 4-tetrahydropyranyl H H3-tetrahydropyranyl 2-CN 6-Cl 3-tetrahydropyranyl H H(R)-3-tetrahydropyranyl 2-CN 6-Cl (R)-3-tetrahydropyranyl H H(S)-3-tetrahydropyranyl 2-CN 6-Cl (S)-3-tetrahydropyranyl H H3-tetrahydrofuranyl 2-CN 6-Cl 3-tetrahydrofuranyl H H(R)-3-tetrahydrofuranyl 2-CN 6-Cl (R)-3-tetrahydrofuranyl H H(S)-3-tetrahydrofuranyl 2-CN 6-Cl (S)-3-tetrahydrofuranyl H H2-pyridinyl 2-CN 6-Cl 2-pyridinyl H H CH₂-2-tetrahydrofuranyl 2-CN 6-ClCH₂-2-tetrahydrofuranyl H H CH₂-2-tetrahydropyranyl 2-CN 6-ClCH₂-2-tetrahydropyranyl H H CH₂OMe 2-CN 6-Cl CH₂OMe H H CH₂CH₂OMe 2-CN6-Cl CH₂CH₂OMe H H CH₂CH₂CH₂OMe 2-CN 6-Cl CH₂CH₂CH₂OMe H H CH₂CH(Me)OMe2-CN 6-Cl CH₂CH(Me)OMe H H CH(Me)OMe 2-CN 6-Cl CH(Me)OMe H H CH(Me)OEt2-CN 6-Cl CH(Me)OEt H H CH(Me)CH₂OMe 2-CN 6-Cl CH(Me)CH₂OMe H HC(Me)₂CH₂OMe 2-CN 6-Cl C(Me)₂CH₂OMe H H CH(Me)CH₂CH₂OMe 2-CN 6-ClCH(Me)CH₂CH₂OMe H H (R)—CH(Me)CH₂OMe 2-CN 6-Cl (R)—CH(Me)CH₂OMe H H(S)-CH(Me)CH₂OMe 2-CN 6-Cl (S)-CH(Me)CH₂OMe H H CH(Me)CH₂OH 2-CN 6-ClCH(Me)CH₂OH H H CH(Me)CH₂OC(═O)Me 2-CN 6-Cl CH(Me)CH₂OC(═O)Me H HCH₂CH₂OCF₃ 2-CN 6-Cl CH₂CH₂OCF₃ H H NH₂ 2-CN 6-Cl NH₂ H H NHCH₃ 2-CN6-Cl NHCH₃ H H NHCH₂CF₃ 2-CN 6-Cl NHCH₂CF₃ H H NHCH₂CH₃ 2-CN 6-ClNHCH₂CH₃ H H NHCH(Me)CH₃ 2-CN 6-Cl NHCH(Me)CH₃ H H NHC(Me)₃ 2-CN 6-ClNHC(Me)₃ H H N(CH₃)₂ 2-CN 6-Cl N(CH₃)₂ H H

TABLE 4

R¹ R^(7a) R^(7b) R^(7c) R¹ R^(7a) R^(7b) R^(7c) Me H 3-F H Me 3-F 4-F HEt H 3-F H Et 3-F 4-F H i-Pr H 3-F H i-Pr 3-F 4-F H n-Pr H 3-F H n-Pr3-F 4-F H i-Bu H 3-F H i-Bu 3-F 4-F H n-Bu H 3-F H n-Bu 3-F 4-F H s-Bu H3-F H s-Bu 3-F 4-F H t-butyl H 3-F H t-butyl 3-F 4-F H n-Hex H 3-F Hn-Hex 3-F 4-F H cyclopropyl H 3-F H cyclopropyl 3-F 4-F H cyclopentyl H3-F H cyclopentyl 3-F 4-F H cyclohexyl H 3-F H cyclohexyl 3-F 4-F H2-cyclohexenyl H 3-F H 2-cyclohexenyl 3-F 4-F H 3-cyclohexenyl H 3-F H3-cyclohexenyl 3-F 4-F H CH-c-Pr H 3-F H CH-c-Pr 3-F 4-F H4-tetrahydropyranyl H 3-F H 4-tetrahydropyranyl 3-F 4-F H3-tetrahydropyranyl H 3-F H 3-tetrahydropyranyl 3-F 4-F H(R)-3-tetrahydropyranyl H 3-F H (R)-3-tetrahydropyranyl 3-F 4-F H(S)-3-tetrahydropyranyl H 3-F H (S)-3-tetrahydropyranyl 3-F 4-F H3-tetrahydrofuranyl H 3-F H 3-tetrahydrofuranyl 3-F 4-F H(R)-3-tetrahydrofuranyl H 3-F H (R)-3-tetrahydrofuranyl 3-F 4-F H(S)-3-tetrahydrofuranyl H 3-F H (S)-3-tetrahydrofuranyl 3-F 4-F H2-pyridinyl H 3-F H 2-pyridinyl 3-F 4-F H 2-pyrimidinyl H 3-F H2-pyrimidinyl 3-F 4-F H 2-pyrazinyl H 3-F H 2-pyrazinyl 3-F 4-F H2-thiazolyl H 3-F H 2-thiazolyl 3-F 4-F H 2-oxazolyl H 3-F H 2-oxazolyl3-F 4-F H 2-chloro-2-propenyl H 3-F H 2-chloro-2-propenyl 3-F 4-F H3,3-dichloro-2-propenyl H 3-F H 3,3-dichloro-2-propenyl 3-F 4-F HCH₂-2-tetrahydrofuranyl H 3-F H CH₂-2-tetrahydrofuranyl 3-F 4-F HCH₂-2-tetrahydropyranyl H 3-F H CH₂-2-tetrahydropyranyl 3-F 4-F HCH₂CH₂OH H 3-F H CH₂CH₂OH 3-F 4-F H CH₂OMe H 3-F H CH₂OMe 3-F 4-F HCH₂CH₂OMe H 3-F H CH₂CH₂OMe 3-F 4-F H CH₂CH₂CH₂OMe H 3-F H CH₂CH₂CH₂OMe3-F 4-F H CH₂CH(Me)OMe H 3-F H CH₂CH(Me)OMe 3-F 4-F H CH(Me)OMe H 3-F HCH(Me)OMe 3-F 4-F H CH(Me)OEt H 3-F H CH(Me)OEt 3-F 4-F H CH(Me)CH₂OMe H3-F H CH(Me)CH₂OMe 3-F 4-F H C(Me)₂CH₂OMe H 3-F H C(Me)₂CH₂OMe 3-F 4-F HCH(Me)CH₂CH₂OMe H 3-F H CH(Me)CH₂CH₂OMe 3-F 4-F H (R)—CH(Me)CH₂OMe H 3-FH (R)—CH(Me)CH₂OMe 3-F 4-F H (S)-CH(Me)CH₂OMe H 3-F H (S)-CH(Me)CH₂OMe3-F 4-F H CH(Me)CH₂OH H 3-F H CH(Me)CH₂OH 3-F 4-F H CH(Me)CH₂OC(═O)Me H3-F H CH(Me)CH₂OC(═O)Me 3-F 4-F H CH(Me)CH(OMe)₂ H 3-F H CH(Me)CH(OMe)₂3-F 4-F H CH₂-2-dioxolanyl H 3-F H CH₂-2-dioxolanyl 3-F 4-F H CH₂CH₂OCF₃H 3-F H CH₂CH₂OCF₃ 3-F 4-F H CH₂CH(Me)SMe H 3-F H CH₂CH(Me)SMe 3-F 4-F HCH₂-2-thienyl H 3-F H CH₂-2-thienyl 3-F 4-F H CH₂-2-pyridinyl H 3-F HCH₂-2-pyridinyl 3-F 4-F H CH₂-3-pyridinyl H 3-F H CH₂-3-pyridinyl 3-F4-F H NH₂ H 3-F H NH₂ 3-F 4-F H NHCH₃ H 3-F H NHCH₃ 3-F 4-F H NHCH₂CF₃ H3-F H NHCH₂CF₃ 3-F 4-F H NHCH₂CH₃ H 3-F H NHCH₂CH₃ 3-F 4-F H NHCH(Me)CH₃H 3-F H NHCH(Me)CH₃ 3-F 4-F H NHCH₂CH(Me)₂ H 3-F H NHCH₂CH(Me)₂ 3-F 4-FH NHC(Me)₃ H 3-F H NHC(Me)₃ 3-F 4-F H N(CH₃)₂ H 3-F H N(CH₃)₂ 3-F 4-F HN(CH₃)CH₂CH₃ H 3-F H N(CH₃)CH₂CH₃ 3-F 4-F H N(CH₂CH₃)CH₂CH₃ H 3-F HN(CH₂CH₃)CH₂CH₃ 3-F 4-F H Me 3-CN 5-F H Me H 3-Cl H Et 3-CN 5-F H Et H3-Cl H i-Pr 3-CN 5-F H i-Pr H 3-Cl H n-Pr 3-CN 5-F H n-Pr H 3-Cl H i-Bu3-CN 5-F H i-Bu H 3-Cl H n-Bu 3-CN 5-F H n-Bu H 3-Cl H s-Bu 3-CN 5-F Hs-Bu H 3-Cl H t-butyl 3-CN 5-F H t-butyl H 3-Cl H n-Hex 3-CN 5-F H n-HexH 3-Cl H cyclopropyl 3-CN 5-F H cyclopropyl H 3-Cl H cyclopentyl 3-CN5-F H cyclopentyl H 3-Cl H cyclohexyl 3-CN 5-F H cyclohexyl H 3-Cl H2-cyclohexenyl 3-CN 5-F H 2-cyclohexenyl H 3-Cl H 3-cyclohexenyl 3-CN5-F H 3-cyclohexenyl H 3-Cl H CH-c-Pr 3-CN 5-F H CH-c-Pr H 3-Cl H4-tetrahydropyranyl 3-CN 5-F H 4-tetrahydropyranyl H 3-Cl H3-tetrahydropyranyl 3-CN 5-F H 3-tetrahydropyranyl H 3-Cl H(R)-3-tetrahydropyranyl 3-CN 5-F H (R)-3-tetrahydropyranyl H 3-Cl H(S)-3-tetrahydropyranyl 3-CN 5-F H (S)-3-tetrahydropyranyl H 3-Cl H3-tetrahydrofuranyl 3-CN 5-F H 3-tetrahydrofuranyl H 3-Cl H(R)-3-tetrahydrofuranyl 3-CN 5-F H (R)-3-tetrahydrofuranyl H 3-Cl H(S)-3-tetrahydrofuranyl 3-CN 5-F H (S)-3-tetrahydrofuranyl H 3-Cl H2-pyridinyl 3-CN 5-F H 2-pyridinyl H 3-Cl H 2-pyrimidinyl 3-CN 5-F H2-pyrimidinyl H 3-Cl H 2-pyrazinyl 3-CN 5-F H 2-pyrazinyl H 3-Cl H2-thiazolyl 3-CN 5-F H 2-thiazolyl H 3-Cl H 2-oxazolyl 3-CN 5-F H2-oxazolyl H 3-Cl H 2-chloro-2-propenyl 3-CN 5-F H 2-chloro-2-propenyl H3-Cl H 3,3-dichloro-2-propenyl 3-CN 5-F H 3,3-dichloro-2-propenyl H 3-ClH CH₂-2-tetrahydrofuranyl 3-CN 5-F H CH₂-2-tetrahydrofuranyl H 3-Cl HCH₂-2-tetrahydropyranyl 3-CN 5-F H CH₂-2-tetrahydropyranyl H 3-Cl HCH₂CH₂OH 3-CN 5-F H CH₂CH₂OH H 3-Cl H CH₂OMe 3-CN 5-F H CH₂OMe H 3-Cl HCH₂CH₂OMe 3-CN 5-F H CH₂CH₂OMe H 3-Cl H CH₂CH₂CH₂OMe 3-CN 5-F HCH₂CH₂CH₂OMe H 3-Cl H CH₂CH(Me)OMe 3-CN 5-F H CH₂CH(Me)OMe H 3-Cl HCH(Me)OMe 3-CN 5-F H CH(Me)OMe H 3-Cl H CH(Me)OEt 3-CN 5-F H CH(Me)OEt H3-Cl H CH(Me)CH₂OMe 3-CN 5-F H CH(Me)CH₂OMe H 3-Cl H C(Me)₂CH₂OMe 3-CN5-F H C(Me)₂CH₂OMe H 3-Cl H CH(Me)CH₂CH₂OMe 3-CN 5-F H CH(Me)CH₂CH₂OMe H3-Cl H (R)—CH(Me)CH₂OMe 3-CN 5-F H (R)—CH(Me)CH₂OMe H 3-Cl H(S)-CH(Me)CH₂OMe 3-CN 5-F H (S)-CH(Me)CH₂OMe H 3-Cl H CH(Me)CH₂OH 3-CN5-F H CH(Me)CH₂OH H 3-Cl H CH(Me)CH₂OC(═O)Me 3-CN 5-F HCH(Me)CH₂OC(═O)Me H 3-Cl H CH(Me)CH(OMe)₂ 3-CN 5-F H CH(Me)CH(OMe)₂ H3-Cl H CH₂-2-dioxolanyl 3-CN 5-F H CH₂-2-dioxolanyl H 3-Cl H CH₂CH₂OCF₃3-CN 5-F H CH₂CH₂OCF₃ H 3-Cl H CH₂CH(Me)SMe 3-CN 5-F H CH₂CH(Me)SMe H3-Cl H CH₂-2-thienyl 3-CN 5-F H CH₂-2-thienyl H 3-Cl H CH₂-2-pyridinyl3-CN 5-F H CH₂-2-pyridinyl H 3-Cl H CH₂-3-pyridinyl 3-CN 5-F HCH₂-3-pyridinyl H 3-Cl H NH₂ 3-CN 5-F H NH₂ H 3-Cl H NHCH₃ 3-CN 5-F HNHCH₃ H 3-Cl H NHCH₂CF₃ 3-CN 5-F H NHCH₂CF₃ H 3-Cl H NHCH₂CH₃ 3-CN 5-F HNHCH₂CH₃ H 3-Cl H NHCH(Me)CH₃ 3-CN 5-F H NHCH(Me)CH₃ H 3-Cl HNHCH₂CH(Me)₂ 3-CN 5-F H NHCH₂CH(Me)₂ H 3-Cl H NHC(Me)₃ 3-CN 5-F HNHC(Me)₃ H 3-Cl H N(CH₃)₂ 3-CN 5-F H N(CH₃)₂ H 3-Cl H N(CH₃)CH₂CH₃ 3-CN5-F H N(CH₃)CH₂CH₃ H 3-Cl H N(CH₂CH₃)CH₂CH₃ 3-CN 5-F H N(CH₂CH₃)CH₂CH₃ H3-Cl H t-butyl H 3-CN H t-butyl H 3-NO₂ H cyclopropyl H 3-CN Hcyclopropyl H 3-NO₂ H cyclohexyl H 3-CN H cyclohexyl H 3-NO₂ H CH-c-Pr H3-CN H CH-c-Pr H 3-NO₂ H 4-tetrahydropyranyl H 3-CN H4-tetrahydropyranyl H 3-NO₂ H 3-tetrahydropyranyl H 3-CN H3-tetrahydropyranyl H 3-NO₂ H (R)-3-tetrahydropyranyl H 3-CN H(R)-3-tetrahydropyranyl H 3-NO₂ H (S)-3-tetrahydropyranyl H 3-CN H(S)-3-tetrahydropyranyl H 3-NO₂ H 3-tetrahydrofuranyl H 3-CN H3-tetrahydrofuranyl H 3-NO₂ H (R)-3-tetrahydrofuranyl H 3-CN H(R)-3-tetrahydrofuranyl H 3-NO₂ H (S)-3-tetrahydrofuranyl H 3-CN H(S)-3-tetrahydrofuranyl H 3-NO₂ H 2-pyridinyl H 3-CN H 2-pyridinyl H3-NO₂ H CH₂-2-tetrahydrofuranyl H 3-CN H CH₂-2-tetrahydrofuranyl H 3-NO₂H CH₂-2-tetrahydropyranyl H 3-CN H CH₂-2-tetrahydropyranyl H 3-NO₂ HCH₂OMe H 3-CN H CH₂OMe H 3-NO₂ H CH₂CH₂OMe H 3-CN H CH₂CH₂OMe H 3-NO₂ HCH₂CH₂CH₂OMe H 3-CN H CH₂CH₂CH₂OMe H 3-NO₂ H CH₂CH(Me)OMe H 3-CN HCH₂CH(Me)OMe H 3-NO₂ H CH(Me)OMe H 3-CN H CH(Me)OMe H 3-NO₂ H CH(Me)OEtH 3-CN H CH(Me)OEt H 3-NO₂ H CH(Me)CH₂OMe H 3-CN H CH(Me)CH₂OMe H 3-NO₂H C(Me)₂CH₂OMe H 3-CN H C(Me)₂CH₂OMe H 3-NO₂ H CH(Me)CH₂CH₂OMe H 3-CN HCH(Me)CH₂CH₂OMe H 3-NO₂ H (R)—CH(Me)CH₂OMe H 3-CN H (R)—CH(Me)CH₂OMe H3-NO₂ H (S)-CH(Me)CH₂OMe H 3-CN H (S)-CH(Me)CH₂OMe H 3-NO₂ H CH(Me)CH₂OHH 3-CN H CH(Me)CH₂OH H 3-NO₂ H CH(Me)CH₂OC(═O)Me H 3-CN HCH(Me)CH₂OC(═O)Me H 3-NO₂ H CH₂CH₂OCF₃ H 3-CN H CH₂CH₂OCF₃ H 3-NO₂ H NH₂H 3-CN H NH₂ H 3-NO₂ H NHCH₃ H 3-CN H NHCH₃ H 3-NO₂ H NHCH₂CF₃ H 3-CN HNHCH₂CF₃ H 3-NO₂ H NHCH₂CH₃ H 3-CN H NHCH₂CH₃ H 3-NO₂ H NHCH(Me)CH₃ H3-CN H NHCH(Me)CH₃ H 3-NO₂ H NHC(Me)₃ H 3-CN H NHC(Me)₃ H 3-NO₂ HN(CH₃)₂ H 3-CN H N(CH₃)₂ H 3-NO₂ H t-butyl H 3-Br H t-butyl H 3-Me Hcyclopropyl H 3-Br H cyclopropyl H 3-Me H cyclohexyl H 3-Br H cyclohexylH 3-Me H CH-c-Pr H 3-Br H CH-c-Pr H 3-Me H 4-tetrahydropyranyl H 3-Br H4-tetrahydropyranyl H 3-Me H 3-tetrahydropyranyl H 3-Br H3-tetrahydropyranyl H 3-Me H (R)-3-tetrahydropyranyl H 3-Br H(R)-3-tetrahydropyranyl H 3-Me H (S)-3-tetrahydropyranyl H 3-Br H(S)-3-tetrahydropyranyl H 3-Me H 3-tetrahydrofuranyl H 3-Br H3-tetrahydrofuranyl H 3-Me H (R)-3-tetrahydrofuranyl H 3-Br H(R)-3-tetrahydrofuranyl H 3-Me H (S)-3-tetrahydrofuranyl H 3-Br H(S)-3-tetrahydrofuranyl H 3-Me H 2-pyridinyl H 3-Br H 2-pyridinyl H 3-MeH CH₂-2-tetrahydrofuranyl H 3-Br H CH₂-2-tetrahydrofuranyl H 3-Me HCH₂-2-tetrahydropyranyl H 3-Br H CH₂-2-tetrahydropyranyl H 3-Me H CH₂OMeH 3-Br H CH₂OMe H 3-Me H CH₂CH₂OMe H 3-Br H CH₂CH₂OMe H 3-Me HCH₂CH₂CH₂OMe H 3-Br H CH₂CH₂CH₂OMe H 3-Me H CH₂CH(Me)OMe H 3-Br HCH₂CH(Me)OMe H 3-Me H CH(Me)OMe H 3-Br H CH(Me)OMe H 3-Me H CH(Me)OEt H3-Br H CH(Me)OEt H 3-Me H CH(Me)CH₂OMe H 3-Br H CH(Me)CH₂OMe H 3-Me HC(Me)₂CH₂OMe H 3-Br H C(Me)₂CH₂OMe H 3-Me H CH(Me)CH₂CH₂OMe H 3-Br HCH(Me)CH₂CH₂OMe H 3-Me H (R)—CH(Me)CH₂OMe H 3-Br H (R)—CH(Me)CH₂OMe H3-Me H (S)-CH(Me)CH₂OMe H 3-Br H (S)-CH(Me)CH₂OMe H 3-Me H CH(Me)CH₂OH H3-Br H CH(Me)CH₂OH H 3-Me H CH(Me)CH₂OC(═O)Me H 3-Br H CH(Me)CH₂OC(═O)MeH 3-Me H CH₂CH₂OCF₃ H 3-Br H CH₂CH₂OCF₃ H 3-Me H NH₂ H 3-Br H NH₂ H 3-MeH NHCH₃ H 3-Br H NHCH₃ H 3-Me H NHCH₂CF₃ H 3-Br H NHCH₂CF₃ H 3-Me HNHCH₂CH₃ H 3-Br H NHCH₂CH₃ H 3-Me H NHCH(Me)CH₃ H 3-Br H NHCH(Me)CH₃ H3-Me H NHC(Me)₃ H 3-Br H NHC(Me)₃ H 3-Me H N(CH₃)₂ H 3-Br H N(CH₃)₂ H3-Me H t-butyl H 4-Me H t-butyl 2-Cl 6-Me H cyclopropyl H 4-Me Hcyclopropyl 2-Cl 6-Me H cyclohexyl H 4-Me H cyclohexyl 2-Cl 6-Me HCH-c-Pr H 4-Me H CH-c-Pr 2-Cl 6-Me H 4-tetrahydropyranyl H 4-Me H4-tetrahydropyranyl 2-Cl 6-Me H 3-tetrahydropyranyl H 4-Me H3-tetrahydropyranyl 2-Cl 6-Me H (R)-3-tetrahydropyranyl H 4-Me H(R)-3-tetrahydropyranyl 2-Cl 6-Me H (S)-3-tetrahydropyranyl H 4-Me H(S)-3-tetrahydropyranyl 2-Cl 6-Me H 3-tetrahydrofuranyl H 4-Me H3-tetrahydrofuranyl 2-Cl 6-Me H (R)-3-tetrahydrofuranyl H 4-Me H(R)-3-tetrahydrofuranyl 2-Cl 6-Me H (S)-3-tetrahydrofuranyl H 4-Me H(S)-3-tetrahydrofuranyl 2-Cl 6-Me H 2-pyridinyl H 4-Me H 2-pyridinyl2-Cl 6-Me H CH₂-2-tetrahydrofuranyl H 4-Me H CH₂-2-tetrahydrofuranyl2-Cl 6-Me H CH₂-2-tetrahydropyranyl H 4-Me H CH₂-2-tetrahydropyranyl2-Cl 6-Me H CH₂OMe H 4-Me H CH₂OMe 2-Cl 6-Me H CH₂CH₂OMe H 4-Me HCH₂CH₂OMe 2-Cl 6-Me H CH₂CH₂CH₂OMe H 4-Me H CH₂CH₂CH₂OMe 2-Cl 6-Me HCH₂CH(Me)OMe H 4-Me H CH₂CH(Me)OMe 2-Cl 6-Me H CH(Me)OMe H 4-Me HCH(Me)OMe 2-Cl 6-Me H CH(Me)OEt H 4-Me H CH(Me)OEt 2-Cl 6-Me HCH(Me)CH₂OMe H 4-Me H CH(Me)CH₂OMe 2-Cl 6-Me H C(Me)₂CH₂OMe H 4-Me HC(Me)₂CH₂OMe 2-Cl 6-Me H CH(Me)CH₂CH₂OMe H 4-Me H CH(Me)CH₂CH₂OMe 2-Cl6-Me H (R)—CH(Me)CH₂OMe H 4-Me H (R)—CH(Me)CH₂OMe 2-Cl 6-Me H(S)-CH(Me)CH₂OMe H 4-Me H (S)-CH(Me)CH₂OMe 2-Cl 6-Me H CH(Me)CH₂OH H4-Me H CH(Me)CH₂OH 2-Cl 6-Me H CH(Me)CH₂OC(═O)Me H 4-Me HCH(Me)CH₂OC(═O)Me 2-Cl 6-Me H CH₂CH₂OCF₃ H 4-Me H CH₂CH₂OCF₃ 2-Cl 6-Me HNH₂ H 4-Me H NH₂ 2-Cl 6-Me H NHCH₃ H 4-Me H NHCH₃ 2-Cl 6-Me H NHCH₂CF₃ H4-Me H NHCH₂CF₃ 2-Cl 6-Me H NHCH₂CH₃ H 4-Me H NHCH₂CH₃ 2-Cl 6-Me HNHCH(Me)CH₃ H 4-Me H NHCH(Me)CH₃ 2-Cl 6-Me H NHC(Me)₃ H 4-Me H NHC(Me)₃2-Cl 6-Me H N(CH₃)₂ H 4-Me H N(CH₃)₂ 2-Cl 6-Me H t-butyl 2-CN 6-Me Ht-butyl 2-Me 6-NO₂ H cyclopropyl 2-CN 6-Me H cyclopropyl 2-Me 6-NO₂ Hcyclohexyl 2-CN 6-Me H cyclohexyl 2-Me 6-NO₂ H CH-c-Pr 2-CN 6-Me HCH-c-Pr 2-Me 6-NO₂ H 4-tetrahydropyranyl 2-CN 6-Me H 4-tetrahydropyranyl2-Me 6-NO₂ H 3-tetrahydropyranyl 2-CN 6-Me H 3-tetrahydropyranyl 2-Me6-NO₂ H (R)-3-tetrahydropyranyl 2-CN 6-Me H (R)-3-tetrahydropyranyl 2-Me6-NO₂ H (S)-3-tetrahydropyranyl 2-CN 6-Me H (S)-3-tetrahydropyranyl 2-Me6-NO₂ H 3-tetrahydrofuranyl 2-CN 6-Me H 3-tetrahydrofuranyl 2-Me 6-NO₂ H(R)-3-tetrahydrofuranyl 2-CN 6-Me H (R)-3-tetrahydrofuranyl 2-Me 6-NO₂ H(S)-3-tetrahydrofuranyl 2-CN 6-Me H (S)-3-tetrahydrofuranyl 2-Me 6-NO₂ H2-pyridinyl 2-CN 6-Me H 2-pyridinyl 2-Me 6-NO₂ H CH₂-2-tetrahydrofuranyl2-CN 6-Me H CH₂-2-tetrahydrofuranyl 2-Me 6-NO₂ H CH₂-2-tetrahydropyranyl2-CN 6-Me H CH₂-2-tetrahydropyranyl 2-Me 6-NO₂ H CH₂OMe 2-CN 6-Me HCH₂OMe 2-Me 6-NO₂ H CH₂CH₂OMe 2-CN 6-Me H CH₂CH₂OMe 2-Me 6-NO₂ HCH₂CH₂CH₂OMe 2-CN 6-Me H CH₂CH₂CH₂OMe 2-Me 6-NO₂ H CH₂CH(Me)OMe 2-CN6-Me H CH₂CH(Me)OMe 2-Me 6-NO₂ H CH(Me)OMe 2-CN 6-Me H CH(Me)OMe 2-Me6-NO₂ H CH(Me)OEt 2-CN 6-Me H CH(Me)OEt 2-Me 6-NO₂ H CH(Me)CH₂OMe 2-CN6-Me H CH(Me)CH₂OMe 2-Me 6-NO₂ H C(Me)₂CH₂OMe 2-CN 6-Me H C(Me)₂CH₂OMe2-Me 6-NO₂ H CH(Me)CH₂CH₂OMe 2-CN 6-Me H CH(Me)CH₂CH₂OMe 2-Me 6-NO₂ H(R)—CH(Me)CH₂OMe 2-CN 6-Me H (R)—CH(Me)CH₂OMe 2-Me 6-NO₂ H(S)-CH(Me)CH₂OMe 2-CN 6-Me H (S)-CH(Me)CH₂OMe 2-Me 6-NO₂ H CH(Me)CH₂OH2-CN 6-Me H CH(Me)CH₂OH 2-Me 6-NO₂ H CH(Me)CH₂OC(═O)Me 2-CN 6-Me HCH(Me)CH₂OC(═O)Me 2-Me 6-NO₂ H CH₂CH₂OCF₃ 2-CN 6-Me H CH₂CH₂OCF₃ 2-Me6-NO₂ H NH₂ 2-CN 6-Me H NH₂ 2-Me 6-NO₂ H NHCH₃ 2-CN 6-Me H NHCH₃ 2-Me6-NO₂ H NHCH₂CF₃ 2-CN 6-Me H NHCH₂CF₃ 2-Me 6-NO₂ H NHCH₂CH₃ 2-CN 6-Me HNHCH₂CH₃ 2-Me 6-NO₂ H NHCH(Me)CH₃ 2-CN 6-Me H NHCH(Me)CH₃ 2-Me 6-NO₂ HNHC(Me)₃ 2-CN 6-Me H NHC(Me)₃ 2-Me 6-NO₂ H N(CH₃)₂ 2-CN 6-Me H N(CH₃)₂2-Me 6-NO₂ H t-butyl 2-Cl 6-F H t-butyl 2-Cl 4-Me 6-Me cyclopropyl 2-Cl6-F H cyclopropyl 2-Cl 4-Me 6-Me cyclohexyl 2-Cl 6-F H cyclohexyl 2-Cl4-Me 6-Me CH-c-Pr 2-Cl 6-F H CH-c-Pr 2-Cl 4-Me 6-Me 4-tetrahydropyranyl2-Cl 6-F H 4-tetrahydropyranyl 2-Cl 4-Me 6-Me 3-tetrahydropyranyl 2-Cl6-F H 3-tetrahydropyranyl 2-Cl 4-Me 6-Me (R)-3-tetrahydropyranyl 2-Cl6-F H (R)-3-tetrahydropyranyl 2-Cl 4-Me 6-Me (S)-3-tetrahydropyranyl2-Cl 6-F H (S)-3-tetrahydropyranyl 2-Cl 4-Me 6-Me 3-tetrahydrofuranyl2-Cl 6-F H 3-tetrahydrofuranyl 2-Cl 4-Me 6-Me (R)-3-tetrahydrofuranyl2-Cl 6-F H (R)-3-tetrahydrofuranyl 2-Cl 4-Me 6-Me(S)-3-tetrahydrofuranyl 2-Cl 6-F H (S)-3-tetrahydrofuranyl 2-Cl 4-Me6-Me 2-pyridinyl 2-Cl 6-F H 2-pyridinyl 2-Cl 4-Me 6-MeCH₂-2-tetrahydrofuranyl 2-Cl 6-F H CH₂-2-tetrahydrofuranyl 2-Cl 4-Me6-Me CH₂-2-tetrahydropyranyl 2-Cl 6-F H CH₂-2-tetrahydropyranyl 2-Cl4-Me 6-Me CH₂OMe 2-Cl 6-F H CH₂OMe 2-Cl 4-Me 6-Me CH₂CH₂OMe 2-Cl 6-F HCH₂CH₂OMe 2-Cl 4-Me 6-Me CH₂CH₂CH₂OMe 2-Cl 6-F H CH₂CH₂CH₂OMe 2-Cl 4-Me6-Me CH₂CH(Me)OMe 2-Cl 6-F H CH₂CH(Me)OMe 2-Cl 4-Me 6-Me CH(Me)OMe 2-Cl6-F H CH(Me)OMe 2-Cl 4-Me 6-Me CH(Me)OEt 2-Cl 6-F H CH(Me)OEt 2-Cl 4-Me6-Me CH(Me)CH₂OMe 2-Cl 6-F H CH(Me)CH₂OMe 2-Cl 4-Me 6-Me C(Me)₂CH₂OMe2-Cl 6-F H C(Me)₂CH₂OMe 2-Cl 4-Me 6-Me CH(Me)CH₂CH₂OMe 2-Cl 6-F HCH(Me)CH₂CH₂OMe 2-Cl 4-Me 6-Me (R)—CH(Me)CH₂OMe 2-Cl 6-F H(R)—CH(Me)CH₂OMe 2-Cl 4-Me 6-Me (S)-CH(Me)CH₂OMe 2-Cl 6-F H(S)-CH(Me)CH₂OMe 2-Cl 4-Me 6-Me CH(Me)CH₂OH 2-Cl 6-F H CH(Me)CH₂OH 2-Cl4-Me 6-Me CH(Me)CH₂OC(═O)Me 2-Cl 6-F H CH(Me)CH₂OC(═O)Me 2-Cl 4-Me 6-MeCH₂CH₂OCF₃ 2-Cl 6-F H CH₂CH₂OCF₃ 2-Cl 4-Me 6-Me NH₂ 2-Cl 6-F H NH₂ 2-Cl4-Me 6-Me NHCH₃ 2-Cl 6-F H NHCH₃ 2-Cl 4-Me 6-Me NHCH₂CF₃ 2-Cl 6-F HNHCH₂CF₃ 2-Cl 4-Me 6-Me NHCH₂CH₃ 2-Cl 6-F H NHCH₂CH₃ 2-Cl 4-Me 6-MeNHCH(Me)CH₃ 2-Cl 6-F H NHCH(Me)CH₃ 2-Cl 4-Me 6-Me NHC(Me)₃ 2-Cl 6-F HNHC(Me)₃ 2-Cl 4-Me 6-Me N(CH₃)₂ 2-Cl 6-F H N(CH₃)₂ 2-Cl 4-Me 6-Met-butyl 2-F 3-F 6-F t-butyl 2-F 4-Me 6-F cyclopropyl 2-F 3-F 6-Fcyclopropyl 2-F 4-Me 6-F cyclohexyl 2-F 3-F 6-F cyclohexyl 2-F 4-Me 6-FCH-c-Pr 2-F 3-F 6-F CH-c-Pr 2-F 4-Me 6-F 4-tetrahydropyranyl 2-F 3-F 6-F4-tetrahydropyranyl 2-F 4-Me 6-F 3-tetrahydropyranyl 2-F 3-F 6-F3-tetrahydropyranyl 2-F 4-Me 6-F (R)-3-tetrahydropyrany l2-F 3-F 6-F(R)-3-tetrahydropyranyl 2-F 4-Me 6-F (S)-3-tetrahydropyranyl 2-F 3-F 6-F(S)-3-tetrahydropyranyl 2-F 4-Me 6-F 3-tetrahydrofuranyl 2-F 3-F 6-F3-tetrahydrofuranyl 2-F 4-Me 6-F (R)-3-tetrahydrofuranyl 2-F 3-F 6-F(R)-3-tetrahydrofuranyl 2-F 4-Me 6-F (S)-3-tetrahydrofuranyl 2-F 3-F 6-F(S)-3-tetrahydrofuranyl 2-F 4-Me 6-F 2-pyridinyl 2-F 3-F 6-F 2-pyridinyl2-F 4-Me 6-F CH₂-2-tetrahydrofuranyl 2-F 3-F 6-F CH₂-2-tetrahydrofuranyl2-F 4-Me 6-F CH₂-2-tetrahydropyranyl 2-F 3-F 6-F CH₂-2-tetrahydropyranyl2-F 4-Me 6-F CH₂OMe 2-F 3-F 6-F CH₂OMe 2-F 4-Me 6-F CH₂CH₂OMe 2-F 3-F6-F CH₂CH₂OMe 2-F 4-Me 6-F CH₂CH₂CH₂OMe 2-F 3-F 6-F CH₂CH₂CH₂OMe 2-F4-Me 6-F CH₂CH(Me)OMe 2-F 3-F 6-F CH₂CH(Me)OMe 2-F 4-Me 6-F CH(Me)OMe2-F 3-F 6-F CH(Me)OMe 2-F 4-Me 6-F CH(Me)OEt 2-F 3-F 6-F CH(Me)OEt 2-F4-Me 6-F CH(Me)CH₂OMe 2-F 3-F 6-F CH(Me)CH₂OMe 2-F 4-Me 6-F C(Me)₂CH₂OMe2-F 3-F 6-F C(Me)₂CH₂OMe 2-F 4-Me 6-F CH(Me)CH₂CH₂OMe 2-F 3-F 6-FCH(Me)CH₂CH₂OMe 2-F 4-Me 6-F (R)—CH(Me)CH₂OMe 2-F 3-F 6-F(R)—CH(Me)CH₂OMe 2-F 4-Me 6-F (S)-CH(Me)CH₂OMe 2-F 3-F 6-F(S)-CH(Me)CH₂OMe 2-F 4-Me 6-F CH(Me)CH₂OH 2-F 3-F 6-F CH(Me)CH₂OH 2-F4-Me 6-F CH(Me)CH₂OC(═O)Me 2-F 3-F 6-F CH(Me)CH₂OC(═O)Me 2-F 4-Me 6-FCH₂CH₂OCF₃ 2-F 3-F 6-F CH₂CH₂OCF₃ 2-F 4-Me 6-F NH₂ 2-F 3-F 6-F NH₂ 2-F4-Me 6-F NHCH₃ 2-F 3-F 6-F NHCH₃ 2-F 4-Me 6-F NHCH₂CF₃ 2-F 3-F 6-FNHCH₂CF₃ 2-F 4-Me 6-F NHCH₂CH₃ 2-F 3-F 6-F NHCH₂CH₃ 2-F 4-Me 6-FNHCH(Me)CH₃ 2-F 3-F 6-F NHCH(Me)CH₃ 2-F 4-Me 6-F NHC(Me)₃ 2-F 3-F 6-FNHC(Me)₃ 2-F 4-Me 6-F N(CH₃)₂ 2-F 3-F 6-F N(CH₃)₂ 2-F 4-Me 6-F t-butyl2-Me 5-Cl 6-Me t-butyl 2-Cl 4-Cl 6-Me cyclopropyl 2-Me 5-Cl 6-Mecyclopropyl 2-Cl 4-Cl 6-Me cyclohexyl 2-Me 5-Cl 6-Me cyclohexyl 2-Cl4-Cl 6-Me CH-c-Pr 2-Me 5-Cl 6-Me CH-c-Pr 2-Cl 4-Cl 6-Me4-tetrahydropyranyl 2-Me 5-Cl 6-Me 4-tetrahydropyranyl 2-Cl 4-Cl 6-Me3-tetrahydropyranyl 2-Me 5-Cl 6-Me 3-tetrahydropyranyl 2-Cl 4-Cl 6-Me(R)-3-tetrahydropyranyl 2-Me 5-Cl 6-Me (R)-3-tetrahydropyranyl 2-Cl 4-Cl6-Me (S)-3-tetrahydropyranyl 2-Me 5-Cl 6-Me (S)-3-tetrahydropyranyl 2-Cl4-Cl 6-Me 3-tetrahydrofuranyl 2-Me 5-Cl 6-Me 3-tetrahydrofuranyl 2-Cl4-Cl 6-Me (R)-3-tetrahydrofuranyl 2-Me 5-Cl 6-Me (R)-3-tetrahydrofuranyl2-Cl 4-Cl 6-Me (S)-3-tetrahydrofuranyl 2-Me 5-Cl 6-Me(S)-3-tetrahydrofuranyl 2-Cl 4-Cl 6-Me 2-pyridinyl 2-Me 5-Cl 6-Me2-pyridinyl 2-Cl 4-Cl 6-Me CH₂-2-tetrahydrofuranyl 2-Me 5-Cl 6-MeCH₂-2-tetrahydrofuranyl 2-Cl 4-Cl 6-Me CH₂-2-tetrahydropyranyl 2-Me 5-Cl6-Me CH₂-2-tetrahydropyranyl 2-Cl 4-Cl 6-Me CH₂OMe 2-Me 5-Cl 6-Me CH₂OMe2-Cl 4-Cl 6-Me CH₂CH₂OMe 2-Me 5-Cl 6-Me CH₂CH₂OMe 2-Cl 4-Cl 6-MeCH₂CH₂CH₂OMe 2-Me 5-Cl 6-Me CH₂CH₂CH₂OMe 2-Cl 4-Cl 6-Me CH₂CH(Me)OMe2-Me 5-Cl 6-Me CH₂CH(Me)OMe 2-Cl 4-Cl 6-Me CH(Me)OMe 2-Me 5-Cl 6-MeCH(Me)OMe 2-Cl 4-Cl 6-Me CH(Me)OEt 2-Me 5-Cl 6-Me CH(Me)OEt 2-Cl 4-Cl6-Me CH(Me)CH₂OMe 2-Me 5-Cl 6-Me CH(Me)CH₂OMe 2-Cl 4-Cl 6-MeC(Me)₂CH₂OMe 2-Me 5-Cl 6-Me C(Me)₂CH₂OMe 2-Cl 4-Cl 6-Me CH(Me)CH₂CH₂OMe2-Me 5-Cl 6-Me CH(Me)CH₂CH₂OMe 2-Cl 4-Cl 6-Me (R)—CH(Me)CH₂OMe 2-Me 5-Cl6-Me (R)—CH(Me)CH₂OMe 2-Cl 4-Cl 6-Me (S)-CH(Me)CH₂OMe 2-Me 5-Cl 6-Me(S)-CH(Me)CH₂OMe 2-Cl 4-Cl 6-Me CH(Me)CH₂OH 2-Me 5-Cl 6-Me CH(Me)CH₂OH2-Cl 4-Cl 6-Me CH(Me)CH₂OC(═O)Me 2-Me 5-Cl 6-Me CH(Me)CH₂OC(═O)Me 2-Cl4-Cl 6-Me CH₂CH₂OCF₃ 2-Me 5-Cl 6-Me CH₂CH₂OCF₃ 2-Cl 4-Cl 6-Me NH₂ 2-Me5-Cl 6-Me NH₂ 2-Cl 4-Cl 6-Me NHCH₃ 2-Me 5-Cl 6-Me NHCH₃ 2-Cl 4-Cl 6-MeNHCH₂CF₃ 2-Me 5-Cl 6-Me NHCH₂CF₃ 2-Cl 4-Cl 6-Me NHCH₂CH₃ 2-Me 5-Cl 6-MeNHCH₂CH₃ 2-Cl 4-Cl 6-Me NHCH(Me)CH₃ 2-Me 5-Cl 6-Me NHCH(Me)CH₃ 2-Cl 4-Cl6-Me NHC(Me)₃ 2-Me 5-Cl 6-Me NHC(Me)₃ 2-Cl 4-Cl 6-Me N(CH₃)₂ 2-Me 5-Cl6-Me N(CH₃)₂ 2-Cl 4-Cl 6-Me t-butyl H H H t-butyl 2-Cl 4-Cl 6-Clcyclopropyl H H H cyclopropyl 2-Cl 4-Cl 6-Cl cyclohexyl H H H cyclohexyl2-Cl 4-Cl 6-Cl CH-c-Pr H H H CH-c-Pr 2-Cl 4-Cl 6-Cl 4-tetrahydropyranylH H H 4-tetrahydropyranyl 2-Cl 4-Cl 6-Cl 3-tetrahydropyranyl H H H3-tetrahydropyranyl 2-Cl 4-Cl 6-Cl (R)-3-tetrahydropyranyl H H H(R)-3-tetrahydropyranyl 2-Cl 4-Cl 6-Cl (S)-3-tetrahydropyranyl H H H(S)-3-tetrahydropyranyl 2-Cl 4-Cl 6-Cl 3-tetrahydrofuranyl H H H3-tetrahydrofuranyl 2-Cl 4-Cl 6-Cl (R)-3-tetrahydrofuranyl H H H(R)-3-tetrahydrofuranyl 2-Cl 4-Cl 6-Cl (S)-3-tetrahydrofuranyl H H H(S)-3-tetrahydrofuranyl 2-Cl 4-Cl 6-Cl 2-pyridinyl H H H 2-pyridinyl2-Cl 4-Cl 6-Cl CH₂-2-tetrahydrofuranyl H H H CH₂-2-tetrahydrofuranyl2-Cl 4-Cl 6-Cl CH₂-2-tetrahydropyranyl H H H CH₂-2-tetrahydropyranyl2-Cl 4-Cl 6-Cl CH₂OMe H H H CH₂OMe 2-Cl 4-Cl 6-Cl CH₂CH₂OMe H H HCH₂CH₂OMe 2-Cl 4-Cl 6-Cl CH₂CH₂CH₂OMe H H H CH₂CH₂CH₂OMe 2-Cl 4-Cl 6-ClCH₂CH(Me)OMe H H H CH₂CH(Me)OMe 2-Cl 4-Cl 6-Cl CH(Me)OMe H H H CH(Me)OMe2-Cl 4-Cl 6-Cl CH(Me)OEt H H H CH(Me)OEt 2-Cl 4-Cl 6-Cl CH(Me)CH₂OMe H HH CH(Me)CH₂OMe 2-Cl 4-Cl 6-Cl C(Me)₂CH₂OMe H H H C(Me)₂CH₂OMe 2-Cl 4-Cl6-Cl CH(Me)CH₂CH₂OMe H H H CH(Me)CH₂CH₂OMe 2-Cl 4-Cl 6-Cl(R)—CH(Me)CH₂OMe H H H (R)—CH(Me)CH₂OMe 2-Cl 4-Cl 6-Cl (S)-CH(Me)CH₂OMeH H H (S)-CH(Me)CH₂OMe 2-Cl 4-Cl 6-Cl CH(Me)CH₂OH H H H CH(Me)CH₂OH 2-Cl4-Cl 6-Cl CH(Me)CH₂OC(═O)Me H H H CH(Me)CH₂OC(═O)Me 2-Cl 4-Cl 6-ClCH₂CH₂OCF₃ H H H CH₂CH₂OCF₃ 2-Cl 4-Cl 6-Cl NH₂ H H H NH₂ 2-Cl 4-Cl 6-ClNHCH₃ H H H NHCH₃ 2-Cl 4-Cl 6-Cl NHCH₂CF₃ H H H NHCH₂CF₃ 2-Cl 4-Cl 6-ClNHCH₂CH₃ H H H NHCH₂CH₃ 2-Cl 4-Cl 6-Cl NHCH(Me)CH₃ H H H NHCH(Me)CH₃2-Cl 4-Cl 6-Cl NHC(Me)₃ H H H NHC(Me)₃ 2-Cl 4-Cl 6-Cl N(CH₃)₂ H H HN(CH₃)₂ 2-Cl 4-Cl 6-Cl

TABLE 5

G R⁸ X Y W Z 3-F—Ph H N CH N N 3-Cl—Ph H N CH N N 3,5-di-F—Ph H N CH N N3,5-di-Cl—Ph H N CH N N 3-CN—Ph H N CH N N 3-NO₂—Ph H N CH N N3-Cl-5-F—Ph H N CH N N 3-F-5-CN—Ph H N CH N N 3-F-5-NO₂—Ph H N CH N N3-Cl-5-CN—Ph H N CH N N 3-Cl-5-NO₂—Ph H N CH N N 3-F-4-Me—Ph H N CH N N3-Cl-4-Me—Ph H N CH N N 3,4,5-tri-F—Ph H N CH N N 3-F—Ph H N CH CH CH3-Cl—Ph H N CH CH CH 2,6-di-F—Ph H N CH CH CH 2,6-di-Cl—Ph H N CH CH CH3-CN—Ph H N CH CH CH 3-NO₂—Ph H N CH CH CH 2-F-6-Me—Ph H N CH CH CH2-F-6-MeO—Ph H N CH CH CH 2-Cl-6-Me—Ph H N CH CH CH 2-Cl-6-MeO—Ph H N CHCH CH 2,6-di-Cl-4-Me—Ph H N CH CH CH 2,4-di-Cl-6-Me—Ph H N CH CH CH2,4,6-tri-Cl—Ph H N CH CH CH 3-F—Ph H CH N CH N 3-F—Ph H N N N CH3-Cl—Ph H N N N CH 3,5-di-F—Ph H N N N CH 3,5-di-Cl—Ph H N N N CH3-CN—Ph H N N N CH 3-NO₂—Ph H N N N CH 3-Cl-5-F—Ph H N N N CH3-F-5-CN—Ph H N N N CH 3-F-5-NO₂—Ph H N N N CH 3-Cl-5-CN—Ph H N N N CH3-Cl-5-NO₂—Ph H N N N CH 3-F-4-Me—Ph H N N N CH 3-Cl-4-Me—Ph H N N N CH3,4,5-tri-F—Ph H N N N CH 3-F—Ph H N CH CH N 3-Cl—Ph H N CH CH N2,6-di-F—Ph H N CH CH N 2,6-di-Cl—Ph H N CH CH N 3-CN—Ph H N CH CH N3-NO₂—Ph H N CH CH N 2-F-6-Me—Ph H N CH CH N 2-F-6-MeO—Ph H N CH CH N2-Cl-6-Me—Ph H N CH CH N 2-Cl-6-MeO—Ph H N CH CH N 2,6-di-Cl-4-Me—Ph H NCH CH N 2,4-di-Cl-6-Me—Ph H N CH CH N 2,4,6-tri-Cl—Ph H N CH CH N 3-F—PhMe N CH N N 3-Cl—Ph H CH N CH N 2,6-di-F—Ph H CH N CH N 2,6-di-Cl—Ph HCH N CH N 3-CN—Ph H CH N CH N 3-NO₂—Ph H CH N CH N 2-F-6-Me—Ph H CH N CHN 2-F-6-MeO—Ph H CH N CH N 2-Cl-6-Me—Ph H CH N CH N 2-Cl-6-MeO—Ph H CH NCH N 2,6-di-Cl-4-Me—Ph H CH N CH N 2,4-di-Cl-6-Me—Ph H CH N CH N2,4,6-tri-Cl—Ph H CH N CH N 3-F—Ph Me N N N CH 3-Cl—Ph Me N N N CH3,5-di-F—Ph Me N N N CH 3,5-di-Cl—Ph Me N N N CH 3-CN—Ph Me N N N CH3-NO₂—Ph Me N N N CH 3-F-5-CN—Ph Me N N N CH 3-F-5-NO₂—Ph Me N N N CH3-Cl-5-CN—Ph Me N N N CH 3-Cl-5-NO₂—Ph Me N N N CH 3-F-4-Me—Ph Me N N NCH 3-Cl-4-Me—Ph Me N N N CH 3,4,5-tri-F—Ph Me N N N CH 3-F—Ph Me N CH CHN 3-Cl—Ph Me N CH CH N 2,6-di-F—Ph Me N CH CH N 2,6-di-Cl—Ph Me N CH CHN 3-CN—Ph Me N CH CH N 3-NO₂—Ph Me N CH CH N 3-Cl—Ph Me N CH N N3,5-di-F—Ph Me N CH N N 3,5-di-Cl—Ph Me N CH N N 3-CN—Ph Me N CH N N3-NO₂—Ph Me N CH N N 3-F-5-CN—Ph Me N CH N N 3-F-5-NO₂—Ph Me N CH N N3-Cl-5-CN—Ph Me N CH N N 3-Cl-5-NO₂—Ph Me N CH N N 3-F-4-Me—Ph Me N CH NN 3-Cl-4-Me—Ph Me N CH N N 3,4,5-tri-F—Ph Me N CH N N 3-F—Ph Me N CH CHCH 3-Cl—Ph Me N CH CH CH 2,6-di-F—Ph Me N CH CH CH 2,6-di-Cl—Ph Me N CHCH CH 3-CN—Ph Me N CH CH CH 3-NO₂—Ph Me N CH CH CH 2-F-6-Me—Ph Me N CHCH CH 2-F-6-MeO—Ph Me N CH CH CH 2-Cl-6-Me—Ph Me N CH CH CH2-Cl-6-MeO—Ph Me N CH CH CH 2,6-di-Cl-4-Me—Ph Me N CH CH CH2,4-di-Cl-6-Me—Ph Me N CH CH CH 2,4,6-tri-Cl—Ph Me N CH CH CH 3-F—Ph MeCH N CH N 3-Cl—Ph Me CH N CH N 2,6-di-F—Ph Me CH N CH N 2,6-di-Cl—Ph MeCH N CH N 3-CN—Ph Me CH N CH N 3-NO₂—Ph Me CH N CH N 2-F-6-Me—Ph Me N CHCH N 2-F-6-MeO—Ph Me N CH CH N 2-Cl-6-Me—Ph Me N CH CH N 2-Cl-6-MeO—PhMe N CH CH N 2,6-di-Cl-4-Me—Ph Me N CH CH N 2,4-di-Cl-6-Me—Ph Me N CH CHN 2,4,6-tri-Cl—Ph Me N CH CH N 2-F-6-Me—Ph Me CH N CH N 2-F-6-MeO—Ph MeCH N CH N 2-Cl-6-Me—Ph Me CH N CH N 2-Cl-6-MeO—Ph Me CH N CH N2,6-di-Cl-4-Me—Ph Me CH N CH N 2,4-di-Cl-6-Me—Ph Me CH N CH N2,4,6-tri-Cl—Ph Me CH N CH N

TABLE 6

R¹ X Y W Z R^(7a) R^(7b) R^(7c) t-butyl N N N CH 3-F H H cyclopropyl N NN CH 3-F H H 4-tetrahydropyranyl N N N CH 3-F H H(R)-3-tetrahydropyranyl N N N CH 3-F H H (S)-3-tetrahydropyranyl N N NCH 3-F H H CH₂OMe N N N CH 3-F H H CH₂CH₂OMe N N N CH 3-F H HCH₂CH₂CH₂OMe N N N CH 3-F H H CH₂CH(Me)OMe N N N CH 3-F H H CH(Me)OMe NN N CH 3-F H H CH(Me)OEt N N N CH 3-F H H CH(Me)CH₂OMe N N N CH 3-F H HC(Me)₂CH₂OMe N N N CH 3-F H H CH(Me)CH₂CH₂OMe N N N CH 3-F H H(R)—CH(Me)CH₂OMe N N N CH 3-F H H (S)—CH(Me)CH₂OMe N N N CH 3-F H HCH(Me)CH₂OC(O)Me N N N CH 3-F H H CH₂CH₂OCF₃ N N N CH 3-F H H t-butyl NN N CH 3-Cl H H cyclopropyl N N N CH 3-Cl H H 4-tetrahydropyranyl N N NCH 3-Cl H H (R)-3-tetrahydropyranyl N N N CH 3-Cl H H(S)-3-tetrahydropyranyl N N N CH 3-Cl H H CH₂OMe N N N CH 3-Cl H HCH₂CH₂OMe N N N CH 3-Cl H H CH₂CH₂CH₂OMe N N N CH 3-Cl H H CH₂CH(Me)OMeN N N CH 3-Cl H H CH(Me)OMe N N N CH 3-Cl H H CH(Me)OEt N N N CH 3-Cl HH CH(Me)CH₂OMe N N N CH 3-Cl H H C(Me)₂CH₂OMe N N N CH 3-Cl H HCH(Me)CH₂CH₂OMe N N N CH 3-Cl H H (R)—CH(Me)CH₂OMe N N N CH 3-Cl H H(S)—CH(Me)CH₂OMe N N N CH 3-Cl H H CH(Me)CH₂OC(O)Me N N N CH 3-Cl H HCH₂CH₂OCF₃ N N N CH 3-Cl H H t-butyl N N N CH 3-CN H H cyclopropyl N N NCH 3-CN H H 4-tetrahydropyranyl N N N CH 3-CN H H(R)-3-tetrahydropyranyl N N N CH 3-CN H H (S)-3-tetrahydropyranyl N N NCH 3-CN H H CH₂OMe N N N CH 3-CN H H CH₂CH₂OMe N N N CH 3-CN H HCH₂CH₂CH₂OMe N N N CH 3-CN H H CH₂CH(Me)OMe N N N CH 3-CN H H CH(Me)OMeN N N CH 3-CN H H CH(Me)OEt N N N CH 3-CN H H CH(Me)CH₂OMe N N N CH 3-CNH H C(Me)₂CH₂OMe N N N CH 3-CN H H CH(Me)CH₂CH₂OMe N N N CH 3-CN H H(R)—CH(Me)CH₂OMe N N N CH 3-CN H H (S)—CH(Me)CH₂OMe N N N CH 3-CN H HCH(Me)CH₂OC(O)Me N N N CH 3-CN H H CH₂CH₂OCF₃ N N N CH 3-CN H H t-butylN N N CH 3-CN 5-F H cyclopropyl N N N CH 3-CN 5-F H 4-tetrahydropyranylN N N CH 3-CN 5-F H (R)-3-tetrahydropyranyl N N N CH 3-CN 5-F H(S)-3-tetrahydropyranyl N N N CH 3-CN 5-F H CH₂OMe N N N CH 3-CN 5-F HCH₂CH₂OMe N N N CH 3-CN 5-F H CH₂CH₂CH₂OMe N N N CH 3-CN 5-F HCH₂CH(Me)OMe N N N CH 3-CN 5-F H CH(Me)OMe N N N CH 3-CN 5-F H CH(Me)OEtN N N CH 3-CN 5-F H CH(Me)CH₂OMe N N N CH 3-CN 5-F H C(Me)₂CH₂OMe N N NCH 3-CN 5-F H CH(Me)CH₂CH₂OMe N N N CH 3-CN 5-F H (R)—CH(Me)CH₂OMe N N NCH 3-CN 5-F H (S)—CH(Me)CH₂OMe N N N CH 3-CN 5-F H CH(Me)CH₂OC(O)Me N NN CH 3-CN 5-F H CH₂CH₂OCF₃ N N N CH 3-CN 5-F H t-butyl N N N CH 3-F 5-FH cyclopropyl N N N CH 3-F 5-F H 4-tetrahydropyranyl N N N CH 3-F 5-F H(R)-3-tetrahydropyranyl N N N CH 3-F 5-F H (S)-3-tetrahydropyranyl N N NCH 3-F 5-F H CH₂OMe N N N CH 3-F 5-F H CH₂CH₂OMe N N N CH 3-F 5-F HCH₂CH₂CH₂OMe N N N CH 3-F 5-F H CH₂CH(Me)OMe N N N CH 3-F 5-F HCH(Me)OMe N N N CH 3-F 5-F H CH(Me)OEt N N N CH 3-F 5-F H CH(Me)CH₂OMe NN N CH 3-F 5-F H C(Me)₂CH₂OMe N N N CH 3-F 5-F H CH(Me)CH₂CH₂OMe N N NCH 3-F 5-F H (R)—CH(Me)CH₂OMe N N N CH 3-F 5-F H (S)—CH(Me)CH₂OMe N N NCH 3-F 5-F H CH(Me)CH₂OC(O)Me N N N CH 3-F 5-F H CH₂CH₂OCF₃ N N N CH 3-F5-F H t-butyl N N N CH 3-Cl 5-F H cyclopropyl N N N CH 3-Cl 5-F H4-tetrahydropyranyl N N N CH 3-Cl 5-F H (R)-3-tetrahydropyranyl N N N CH3-Cl 5-F H (S)-3-tetrahydropyranyl N N N CH 3-Cl 5-F H CH₂OMe N N N CH3-Cl 5-F H CH₂CH₂OMe N N N CH 3-Cl 5-F H CH₂CH₂CH₂OMe N N N CH 3-Cl 5-FH CH₂CH(Me)OMe N N N CH 3-Cl 5-F H CH(Me)OMe N N N CH 3-Cl 5-F HCH(Me)OEt N N N CH 3-Cl 5-F H CH(Me)CH₂OMe N N N CH 3-Cl 5-F HC(Me)₂CH₂OMe N N N CH 3-Cl 5-F H CH(Me)CH₂CH₂OMe N N N CH 3-Cl 5-F H(R)—CH(Me)CH₂OMe N N N CH 3-Cl 5-F H (S)—CH(Me)CH₂OMe N N N CH 3-Cl 5-FH CH(Me)CH₂OC(O)Me N N N CH 3-Cl 5-F H CH₂CH₂OCF₃ N N N CH 3-Cl 5-F Ht-butyl N N N CH 3-Cl 5-Cl H cyclopropyl N N N CH 3-Cl 5-Cl H4-tetrahydropyranyl N N N CH 3-Cl 5-Cl H (R)-3-tetrahydropyranyl N N NCH 3-Cl 5-Cl H (S)-3-tetrahydropyranyl N N N CH 3-Cl 5-Cl H CH₂OMe N N NCH 3-Cl 5-Cl H CH₂CH₂OMe N N N CH 3-Cl 5-Cl H CH₂CH₂CH₂OMe N N N CH 3-Cl5-Cl H CH₂CH(Me)OMe N N N CH 3-Cl 5-Cl H CH(Me)OMe N N N CH 3-Cl 5-Cl HCH(Me)OEt N N N CH 3-Cl 5-Cl H CH(Me)CH₂OMe N N N CH 3-Cl 5-Cl HC(Me)₂CH₂OMe N N N CH 3-Cl 5-Cl H CH(Me)CH₂CH₂OMe N N N CH 3-Cl 5-Cl H(R)—CH(Me)CH₂OMe N N N CH 3-Cl 5-Cl H (S)—CH(Me)CH₂OMe N N N CH 3-Cl5-Cl H CH(Me)CH₂OC(O)Me N N N CH 3-Cl 5-Cl H CH₂CH₂OCF₃ N N N CH 3-Cl5-Cl H t-butyl N CH CH N 3-F H H cyclopropyl N CH CH N 3-F H H4-tetrahydropyranyl N CH CH N 3-F H H (R)-3-tetrahydropyranyl N CH CH N3-F H H (S)-3-tetrahydropyranyl N CH CH N 3-F H H CH₂OMe N CH CH N 3-F HH CH₂CH₂OMe N CH CH N 3-F H H CH₂CH₂CH₂OMe N CH CH N 3-F H HCH₂CH(Me)OMe N CH CH N 3-F H H CH(Me)OMe N CH CH N 3-F H H CH(Me)OEt NCH CH N 3-F H H CH(Me)CH₂OMe N CH CH N 3-F H H C(Me)₂CH₂OMe N CH CH N3-F H H CH(Me)CH₂CH₂OMe N CH CH N 3-F H H (R)—CH(Me)CH₂OMe N CH CH N 3-FH H (S)—CH(Me)CH₂OMe N CH CH N 3-F H H CH(Me)CH₂OC(O)Me N CH CH N 3-F HH CH₂CH₂OCF₃ N CH CH N 3-F H H t-butyl N CH CH N 3-Cl H H cyclopropyl NCH CH N 3-Cl H H 4-tetrahydropyranyl N CH CH N 3-Cl H H(R)-3-tetrahydropyranyl N CH CH N 3-Cl H H (S)-3-tetrahydropyranyl N CHCH N 3-Cl H H CH₂OMe N CH CH N 3-Cl H H CH₂CH₂OMe N CH CH N 3-Cl H HCH₂CH₂CH₂OMe N CH CH N 3-Cl H H CH₂CH(Me)OMe N CH CH N 3-Cl H HCH(Me)OMe N CH CH N 3-Cl H H CH(Me)OEt N CH CH N 3-Cl H H CH(Me)CH₂OMe NCH CH N 3-Cl H H C(Me)₂CH₂OMe N CH CH N 3-Cl H H CH(Me)CH₂CH₂OMe N CH CHN 3-Cl H H (R)—CH(Me)CH₂OMe N CH CH N 3-Cl H H (S)—CH(Me)CH₂OMe N CH CHN 3-Cl H H CH(Me)CH₂OC(O)Me N CH CH N 3-Cl H H CH₂CH₂OCF₃ N CH CH N 3-ClH H t-butyl N CH CH N 2-Cl 6-Me H cyclopropyl N CH CH N 2-Cl 6-Me H4-tetrahydropyranyl N CH CH N 2-Cl 6-Me H (R)-3-tetrahydropyranyl N CHCH N 2-Cl 6-Me H (S)-3-tetrahydropyranyl N CH CH N 2-Cl 6-Me H CH₂OMe NCH CH N 2-Cl 6-Me H CH₂CH₂OMe N CH CH N 2-Cl 6-Me H CH₂CH₂CH₂OMe N CH CHN 2-Cl 6-Me H CH₂CH(Me)OMe N CH CH N 2-Cl 6-Me H CH(Me)OMe N CH CH N2-Cl 6-Me H CH(Me)OEt N CH CH N 2-Cl 6-Me H CH(Me)CH₂OMe N CH CH N 2-Cl6-Me H C(Me)₂CH₂OMe N CH CH N 2-Cl 6-Me H CH(Me)CH₂CH₂OMe N CH CH N 2-Cl6-Me H (R)—CH(Me)CH₂OMe N CH CH N 2-Cl 6-Me H (S)—CH(Me)CH₂OMe N CH CH N2-Cl 6-Me H CH(Me)CH₂OC(O)Me N CH CH N 2-Cl 6-Me H CH₂CH₂OCF₃ N CH CH N2-Cl 6-Me H t-butyl N CH CH N 2-Cl 6-Cl H cyclopropyl N CH CH N 2-Cl6-Cl H 4-tetrahydropyranyl N CH CH N 2-Cl 6-Cl H (R)-3-tetrahydropyranylN CH CH N 2-Cl 6-Cl H (S)-3-tetrahydropyranyl N CH CH N 2-Cl 6-Cl HCH₂OMe N CH CH N 2-Cl 6-Cl H CH₂CH₂OMe N CH CH N 2-Cl 6-Cl HCH₂CH₂CH₂OMe N CH CH N 2-Cl 6-Cl H CH₂CH(Me)OMe N CH CH N 2-Cl 6-Cl HCH(Me)OMe N CH CH N 2-Cl 6-Cl H CH(Me)OEt N CH CH N 2-Cl 6-Cl HCH(Me)CH₂OMe N CH CH N 2-Cl 6-Cl H C(Me)₂CH₂OMe N CH CH N 2-Cl 6-Cl HCH(Me)CH₂CH₂OMe N CH CH N 2-Cl 6-Cl H (R)—CH(Me)CH₂OMe N CH CH N 2-Cl6-Cl H (S)—CH(Me)CH₂OMe N CH CH N 2-Cl 6-Cl H CH(Me)CH₂OC(O)Me N CH CH N2-Cl 6-Cl H CH₂CH₂OCF₃ N CH CH N 2-Cl 6-Cl H t-butyl N CH CH N 2-Cl 4-Cl6-Me cyclopropyl N CH CH N 2-Cl 4-Cl 6-Me 4-tetrahydropyranyl N CH CH N2-Cl 4-Cl 6-Me (R)-3-tetrahydropyranyl N CH CH N 2-Cl 4-Cl 6-Me(S)-3-tetrahydropyranyl N CH CH N 2-Cl 4-Cl 6-Me CH₂OMe N CH CH N 2-Cl4-Cl 6-Me CH₂CH₂OMe N CH CH N 2-Cl 4-Cl 6-Me CH₂CH₂CH₂OMe N CH CH N 2-Cl4-Cl 6-Me CH₂CH(Me)OMe N CH CH N 2-Cl 4-Cl 6-Me CH(Me)OMe N CH CH N 2-Cl4-Cl 6-Me CH(Me)OEt N CH CH N 2-Cl 4-Cl 6-Me CH(Me)CH₂OMe N CH CH N 2-Cl4-Cl 6-Me C(Me)₂CH₂OMe N CH CH N 2-Cl 4-Cl 6-Me CH(Me)CH₂CH₂OMe N CH CHN 2-Cl 4-Cl 6-Me (R)—CH(Me)CH₂OMe N CH CH N 2-Cl 4-Cl 6-Me(S)—CH(Me)CH₂OMe N CH CH N 2-Cl 4-Cl 6-Me CH(Me)CH₂OC(O)Me N CH CH N2-Cl 4-Cl 6-Me CH₂CH₂OCF₃ N CH CH N 2-Cl 4-Cl 6-Me t-butyl CH N N CH 3-FH H cyclopropyl CH N N CH 3-F H H 4-tetrahydropyranyl CH N N CH 3-F H H(R)-3-tetrahydropyranyl CH N N CH 3-F H H (S)-3-tetrahydropyranyl CH N NCH 3-F H H CH₂OMe CH N N CH 3-F H H CH₂CH₂OMe CH N N CH 3-F H HCH₂CH₂CH₂OMe CH N N CH 3-F H H CH₂CH(Me)OMe CH N N CH 3-F H H CH(Me)OMeCH N N CH 3-F H H CH(Me)OEt CH N N CH 3-F H H CH(Me)CH₂OMe CH N N CH 3-FH H C(Me)₂CH₂OMe CH N N CH 3-F H H CH(Me)CH₂CH₂OMe CH N N CH 3-F H H(R)—CH(Me)CH₂OMe CH N N CH 3-F H H (S)—CH(Me)CH₂OMe CH N N CH 3-F H HCH(Me)CH₂OC(O)Me CH N N CH 3-F H H CH₂CH₂OCF₃ CH N N CH 3-F H H t-butylCH N N CH 3-Cl H H cyclopropyl CH N N CH 3-Cl H H 4-tetrahydropyranyl CHN N CH 3-Cl H H (R)-3-tetrahydropyranyl CH N N CH 3-Cl H H(S)-3-tetrahydropyranyl CH N N CH 3-Cl H H CH₂OMe CH N N CH 3-Cl H HCH₂CH₂OMe CH N N CH 3-Cl H H CH₂CH₂CH₂OMe CH N N CH 3-Cl H HCH₂CH(Me)OMe CH N N CH 3-Cl H H CH(Me)OMe CH N N CH 3-Cl H H CH(Me)OEtCH N N CH 3-Cl H H CH(Me)CH₂OMe CH N N CH 3-Cl H H C(Me)₂CH₂OMe CH N NCH 3-Cl H H CH(Me)CH₂CH₂OMe CH N N CH 3-Cl H H (R)—CH(Me)CH₂OMe CH N NCH 3-Cl H H (S)—CH(Me)CH₂OMe CH N N CH 3-Cl H H CH(Me)CH₂OC(O)Me CH N NCH 3-Cl H H CH₂CH₂OCF₃ CH N N CH 3-Cl H H t-butyl CH N N CH 2-Cl 6-Me Hcyclopropyl CH N N CH 2-Cl 6-Me H 4-tetrahydropyranyl CH N N CH 2-Cl6-Me H (R)-3-tetrahydropyranyl CH N N CH 2-Cl 6-Me H(S)-3-tetrahydropyranyl CH N N CH 2-Cl 6-Me H CH₂OMe CH N N CH 2-Cl 6-MeH CH₂CH₂OMe CH N N CH 2-Cl 6-Me H CH₂CH₂CH₂OMe CH N N CH 2-Cl 6-Me HCH₂CH(Me)OMe CH N N CH 2-Cl 6-Me H CH(Me)OMe CH N N CH 2-Cl 6-Me HCH(Me)OEt CH N N CH 2-Cl 6-Me H CH(Me)CH₂OMe CH N N CH 2-Cl 6-Me HC(Me)₂CH₂OMe CH N N CH 2-Cl 6-Me H CH(Me)CH₂CH₂OMe CH N N CH 2-Cl 6-Me H(R)—CH(Me)CH₂OMe CH N N CH 2-Cl 6-Me H (S)—CH(Me)CH₂OMe CH N N CH 2-Cl6-Me H CH(Me)CH₂OC(O)Me CH N N CH 2-Cl 6-Me H CH₂CH₂OCF₃ CH N N CH 2-Cl6-Me H t-butyl CH N N CH 2-Cl 6-Cl H cyclopropyl CH N N CH 2-Cl 6-Cl H4-tetrahydropyranyl CH N N CH 2-Cl 6-Cl H (R)-3-tetrahydropyranyl CH N NCH 2-Cl 6-Cl H (S)-3-tetrahydropyranyl CH N N CH 2-Cl 6-Cl H CH₂OMe CH NN CH 2-Cl 6-Cl H CH₂CH₂OMe CH N N CH 2-Cl 6-Cl H CH₂CH₂CH₂OMe CH N N CH2-Cl 6-Cl H CH₂CH(Me)OMe CH N N CH 2-Cl 6-Cl H CH(Me)OMe CH N N CH 2-Cl6-Cl H CH(Me)OEt CH N N CH 2-Cl 6-Cl H CH(Me)CH₂OMe CH N N CH 2-Cl 6-ClH C(Me)₂CH₂OMe CH N N CH 2-Cl 6-Cl H CH(Me)CH₂CH₂OMe CH N N CH 2-Cl 6-ClH (R)—CH(Me)CH₂OMe CH N N CH 2-Cl 6-Cl H (S)—CH(Me)CH₂OMe CH N N CH 2-Cl6-Cl H CH(Me)CH₂OC(O)Me CH N N CH 2-Cl 6-Cl H CH₂CH₂OCF₃ CH N N CH 2-Cl6-Cl H t-butyl CH N N CH 2-Cl 4-Cl 6-Me cyclopropyl CH N N CH 2-Cl 4-Cl6-Me 4-tetrahydropyranyl CH N N CH 2-Cl 4-Cl 6-Me(R)-3-tetrahydropyranyl CH N N CH 2-Cl 4-Cl 6-Me (S)-3-tetrahydropyranylCH N N CH 2-Cl 4-Cl 6-Me CH₂OMe CH N N CH 2-Cl 4-Cl 6-Me CH₂CH₂OMe CH NN CH 2-Cl 4-Cl 6-Me CH₂CH₂CH₂OMe CH N N CH 2-Cl 4-Cl 6-Me CH₂CH(Me)OMeCH N N CH 2-Cl 4-Cl 6-Me CH(Me)OMe CH N N CH 2-Cl 4-Cl 6-Me CH(Me)OEt CHN N CH 2-Cl 4-Cl 6-Me CH(Me)CH₂OMe CH N N CH 2-Cl 4-Cl 6-Me C(Me)₂CH₂OMeCH N N CH 2-Cl 4-Cl 6-Me CH(Me)CH₂CH₂OMe CH N N CH 2-Cl 4-Cl 6-Me(R)—CH(Me)CH₂OMe CH N N CH 2-Cl 4-Cl 6-Me (S)—CH(Me)CH₂OMe CH N N CH2-Cl 4-Cl 6-Me CH(Me)CH₂OC(O)Me CH N N CH 2-Cl 4-Cl 6-Me CH₂CH₂OCF₃ CH NN CH 2-Cl 4-Cl 6-Me

TABLE 7

R¹ X Y W Z R⁷ t-butyl CH N N CH 2-Cl cyclopropyl CH N N CH 2-Cl4-tetrahydropyranyl CH N N CH 2-Cl (R)-3-tetrahydropyranyl CH N N CH2-Cl (S)-3-tetrahydropyranyl CH N N CH 2-Cl CH₂OMe CH N N CH 2-ClCH₂CH₂OMe CH N N CH 2-Cl CH₂CH₂CH₂OMe CH N N CH 2-Cl CH₂CH(Me)OMe CH N NCH 2-Cl CH(Me)OMe CH N N CH 2-Cl CH(Me)OEt CH N N CH 2-Cl CH(Me)CH₂OMeCH N N CH 2-Cl C(Me)₂CH₂OMe CH N N CH 2-Cl CH(Me)CH₂CH₂OMe CH N N CH2-Cl (R)—CH(Me)CH₂OMe CH N N CH 2-Cl (S)—CH(Me)CH₂OMe CH N N CH 2-ClCH(Me)CH₂OC(O)Me CH N N CH 2-Cl CH₂CH₂OCF₃ CH N N CH 2-Cl t-butyl N CH NN 2-Cl cyclopropyl N CH N N 2-Cl t-butyl N CH CH CH 2-Cl cyclopropyl NCH CH CH 2-Cl 4-tetrahydropyranyl N CH CH CH 2-Cl(R)-3-tetrahydropyranyl N CH CH CH 2-Cl (S)-3-tetrahydropyranyl N CH CHCH 2-Cl CH₂OMe N CH CH CH 2-Cl CH₂CH₂OMe N CH CH CH 2-Cl CH₂CH₂CH₂OMe NCH CH CH 2-Cl CH₂CH(Me)OMe N CH CH CH 2-Cl CH(Me)OMe N CH CH CH 2-ClCH(Me)OEt N CH CH CH 2-Cl CH(Me)CH₂OMe N CH CH CH 2-Cl C(Me)₂CH₂OMe N CHCH CH 2-Cl CH(Me)CH₂CH₂OMe N CH CH CH 2-Cl (R)—CH(Me)CH₂OMe N CH CH CH2-Cl (S)—CH(Me)CH₂OMe N CH CH CH 2-Cl CH(Me)CH₂OC(O)Me N CH CH CH 2-ClCH₂CH₂OCF₃ N CH CH CH 2-Cl t-butyl CH N N CH 2-Me cyclopropyl CH N N CH2-Me 4-tetrahydropyranyl N CH N N 2-Cl (R)-3-tetrahydropyranyl N CH N N2-Cl (S)-3-tetrahydropyranyl N CH N N 2-Cl CH₂OMe N CH N N 2-ClCH₂CH₂OMe N CH N N 2-Cl CH₂CH₂CH₂OMe N CH N N 2-Cl CH₂CH(Me)OMe N CH N N2-Cl CH(Me)OMe N CH N N 2-Cl CH(Me)OEt N CH N N 2-Cl CH(Me)CH₂OMe N CH NN 2-Cl C(Me)₂CH₂OMe N CH N N 2-Cl CH(Me)CH₂CH₂OMe N CH N N 2-Cl(R)—CH(Me)CH₂OMe N CH N N 2-Cl (S)—CH(Me)CH₂OMe N CH N N 2-ClCH(Me)CH₂OC(O)Me N CH N N 2-Cl CH₂CH₂OCF₃ N CH N N 2-Cl t-butyl N CH CHCH 2-Me cyclopropyl N CH CH CH 2-Me 4-tetrahydropyranyl N CH CH CH 2-Me(R)-3-tetrahydropyranyl N CH CH CH 2-Me (S)-3-tetrahydropyranyl N CH CHCH 2-Me CH₂OMe N CH CH CH 2-Me CH₂CH₂OMe N CH CH CH 2-Me CH₂CH₂CH₂OMe NCH CH CH 2-Me CH₂CH(Me)OMe N CH CH CH 2-Me CH(Me)OMe N CH CH CH 2-MeCH(Me)OEt N CH CH CH 2-Me CH(Me)CH₂OMe N CH CH CH 2-Me C(Me)₂CH₂OMe N CHCH CH 2-Me CH(Me)CH₂CH₂OMe N CH CH CH 2-Me (R)—CH(Me)CH₂OMe N CH CH CH2-Me (S)—CH(Me)CH₂OMe N CH CH CH 2-Me 4-tetrahydropyranyl CH N N CH 2-Me(R)-3-tetrahydropyranyl CH N N CH 2-Me (S)-3-tetrahydropyranyl CH N N CH2-Me CH₂OMe CH N N CH 2-Me CH₂CH₂OMe CH N N CH 2-Me CH₂CH₂CH₂OMe CH N NCH 2-Me CH₂CH(Me)OMe CH N N CH 2-Me CH(Me)OMe CH N N CH 2-Me CH(Me)OEtCH N N CH 2-Me CH(Me)CH₂OMe CH N N CH 2-Me C(Me)₂CH₂OMe CH N N CH 2-MeCH(Me)CH₂CH₂OMe CH N N CH 2-Me (R)—CH(Me)CH₂OMe CH N N CH 2-Me(S)—CH(Me)CH₂OMe CH N N CH 2-Me CH(Me)CH₂OC(O)Me CH N N CH 2-MeCH₂CH₂OCF₃ CH N N CH 2-Me t-butyl N CH N N 2-Me cyclopropyl N CH N N2-Me 4-tetrahydropyranyl N CH N N 2-Me (R)-3-tetrahydropyranyl N CH N N2-Me (S)-3-tetrahydropyranyl N CH N N 2-Me CH₂OMe N CH N N 2-MeCH₂CH₂OMe N CH N N 2-Me CH₂CH₂CH₂OMe N CH N N 2-Me CH₂CH(Me)OMe N CH N N2-Me CH(Me)OMe N CH N N 2-Me CH(Me)OEt N CH N N 2-Me CH(Me)CH₂OMe N CH NN 2-Me C(Me)₂CH₂OMe N CH N N 2-Me CH(Me)CH₂CH₂OMe N CH N N 2-Me(R)—CH(Me)CH₂OMe N CH N N 2-Me (S)—CH(Me)CH₂OMe N CH N N 2-MeCH(Me)CH₂OC(O)Me N CH CH CH 2-Me CH₂CH₂OCF₃ N CH CH CH 2-Me t-butyl N CHCH CH 3-Cl cyclopropyl N CH CH CH 3-Cl 4-tetrahydropyranyl N CH CH CH3-Cl (R)-3-tetrahydropyranyl N CH CH CH 3-Cl (S)-3-tetrahydropyranyl NCH CH CH 3-Cl CH₂OMe N CH CH CH 3-Cl CH₂CH₂OMe N CH CH CH 3-ClCH₂CH₂CH₂OMe N CH CH CH 3-Cl CH₂CH(Me)OMe N CH CH CH 3-Cl CH(Me)OMe N CHCH CH 3-Cl CH(Me)OEt N CH CH CH 3-Cl CH(Me)CH₂OMe N CH CH CH 3-ClC(Me)₂CH₂OMe N CH CH CH 3-Cl CH(Me)CH₂CH₂OMe N CH CH CH 3-Cl(R)—CH(Me)CH₂OMe N CH CH CH 3-Cl (S)—CH(Me)CH₂OMe N CH CH CH 3-ClCH(Me)CH₂OC(O)Me N CH CH CH 3-Cl CH₂CH₂OCF₃ N CH CH CH 3-Cl t-butyl N CHCH CH 3-F cyclopropyl N CH CH CH 3-F 4-tetrahydropyranyl N CH CH CH 3-F(R)-3-tetrahydropyranyl N CH CH CH 3-F (S)-3-tetrahydropyranyl N CH CHCH 3-F CH₂OMe N CH CH CH 3-F CH₂CH₂OMe N CH CH CH 3-F CH₂CH₂CH₂OMe N CHCH CH 3-F CH₂CH(Me)OMe N CH CH CH 3-F CH(Me)OMe N CH CH CH 3-FCH(Me)CH₂OC(O)Me N CH N N 2-Me CH₂CH₂OCF₃ N CH N N 2-Me t-butyl N CH N N3-Cl cyclopropyl N CH N N 3-Cl 4-tetrahydropyranyl N CH N N 3-Cl(R)-3-tetrahydropyranyl N CH N N 3-Cl (S)-3-tetrahydropyranyl N CH N N3-Cl CH₂OMe N CH N N 3-Cl CH₂CH₂OMe N CH N N 3-Cl CH₂CH₂CH₂OMe N CH N N3-Cl CH₂CH(Me)OMe N CH N N 3-Cl CH(Me)OMe N CH N N 3-Cl CH(Me)OEt N CH NN 3-Cl CH(Me)CH₂OMe N CH N N 3-Cl C(Me)₂CH₂OMe N CH N N 3-ClCH(Me)CH₂CH₂OMe N CH N N 3-Cl (R)—CH(Me)CH₂OMe N CH N N 3-Cl(S)—CH(Me)CH₂OMe N CH N N 3-Cl CH(Me)CH₂OC(O)Me N CH N N 3-Cl CH₂CH₂OCF₃N CH N N 3-Cl t-butyl N CH N N 3-F cyclopropyl N CH N N 3-F4-tetrahydropyranyl N CH N N 3-F (R)-3-tetrahydropyranyl N CH N N 3-F(S)-3-tetrahydropyranyl N CH N N 3-F CH₂OMe N CH N N 3-F CH₂CH₂OMe N CHN N 3-F CH₂CH₂CH₂OMe N CH N N 3-F CH₂CH(Me)OMe N CH N N 3-F CH(Me)OMe NCH N N 3-F CH(Me)OEt N CH CH CH 3-F CH(Me)CH₂OMe N CH CH CH 3-FC(Me)₂CH₂OMe N CH CH CH 3-F CH(Me)CH₂CH₂OMe N CH CH CH 3-F(R)—CH(Me)CH₂OMe N CH CH CH 3-F (S)—CH(Me)CH₂OMe N CH CH CH 3-FCH(Me)CH₂OC(O)Me N CH CH CH 3-F CH₂CH₂OCF₃ N CH CH CH 3-F t-butyl N N CHN 3-F cyclopropyl N N CH N 2-F 4-tetrahydropyranyl N N CH N 3-F(R)-3-tetrahydropyranyl N N CH N 2-F (S)-3-tetrahydropyranyl N N CH N3-F CH₂OMe N N CH N 2-F CH₂CH₂OMe N N CH N 3-F CH₂CH₂CH₂OMe N N CH N 2-FCH₂CH(Me)OMe N N CH N 3-F CH(Me)OMe N N CH N 2-F CH(Me)OEt N N CH N 3-FCH(Me)CH₂OMe N N CH N 2-F C(Me)₂CH₂OMe N N CH N 3-F CH(Me)CH₂CH₂OMe N NCH N 2-F (R)—CH(Me)CH₂OMe N N CH N 3-F (S)—CH(Me)CH₂OMe N N CH N 2-FCH(Me)CH₂OC(O)Me N N CH N 3-F CH₂CH₂OCF₃ N N CH N 2-F CH(Me)OEt N CH N N3-F CH(Me)CH₂OMe N CH N N 3-F C(Me)₂CH₂OMe N CH N N 3-F CH(Me)CH₂CH₂OMeN CH N N 3-F (R)—CH(Me)CH₂OMe N CH N N 3-F (S)—CH(Me)CH₂OMe N CH N N 3-FCH(Me)CH₂OC(O)Me N CH N N 3-F CH₂CH₂OCF₃ N CH N N 3-F t-butyl N CH N N —cyclopropyl N CH N N — 4-tetrahydropyranyl N CH N N —(R)-3-tetrahydropyranyl N CH N N — (S)-3-tetrahydropyranyl N CH N N —CH₂OMe N CH N N — CH₂CH₂OMe N CH N N — CH₂CH₂CH₂OMe N CH N N —CH₂CH(Me)OMe N CH N N — CH(Me)OMe N CH N N — CH(Me)OEt N CH N N —CH(Me)CH₂OMe N CH N N — C(Me)₂CH₂OMe N CH N N — CH(Me)CH₂CH₂OMe N CH N N— (R)—CH(Me)CH₂OMe N CH N N — (S)—CH(Me)CH₂OMe N CH N N —CH(Me)CH₂OC(O)Me N CH N N — CH₂CH₂OCF₃ N CH N N — A dash (—) in the R⁷column means that no R⁷ substituent is present.Formulation/Utility

A compound of this invention will generally be used as a fungicidalactive ingredient in a composition, i.e., formulation, with at least oneadditional component selected from the group consisting of surfactants,solid diluents and liquid diluents, which serve as a carrier. Theformulation or composition ingredients are selected to be consistentwith the physical properties of the active ingredient, mode ofapplication and environmental factors such as soil type, moisture andtemperature.

Useful formulations include both liquid and solid compositions. Liquidcompositions include solutions (including emulsifiable concentrates),suspensions, emulsions (including microemulsions and/or suspoemulsions)and the like, which optionally can be thickened into gels. The generaltypes of aqueous liquid compositions are soluble concentrate, suspensionconcentrate, capsule suspension, concentrated emulsion, microemulsionand suspo-emulsion. The general types of nonaqueous liquid compositionsare emulsifiable concentrate, microemulsifiable concentrate, dispersibleconcentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules,pellets, pills, pastilles, tablets, filled films (including seedcoatings) and the like, which can be water-dispersible (“wettable”) orwater-soluble. Films and coatings formed from film-forming solutions orflowable suspensions are particularly useful for seed treatment. Activeingredient can be (micro)encapsulated and further formed into asuspension or solid formulation; alternatively the entire formulation ofactive ingredient can be encapsulated (or “overcoated”). Encapsulationcan control or delay release of the active ingredient. An emulsifiablegranule combines the advantages of both an emulsifiable concentrateformulation and a dry granular formulation. High-strength compositionsare primarily used as intermediates for further formulation.

Sprayable formulations are typically extended in a suitable mediumbefore spraying. Such liquid and solid formulations are formulated to bereadily diluted in the spray medium, usually water. Spray volumes canrange from about from about one to several thousand liters per hectare,but more typically are in the range from about ten to several hundredliters per hectare. Sprayable formulations can be tank mixed with wateror another suitable medium for foliar treatment by aerial or groundapplication, or for application to the growing medium of the plant.Liquid and dry formulations can be metered directly into drip irrigationsystems or metered into the furrow during planting. Liquid and solidformulations can be applied onto vegetable seeds as seed treatmentsbefore planting to protect developing roots and other subterranean plantparts and/or foliage through systemic uptake.

The formulations will typically contain effective amounts of activeingredient, diluent and surfactant within the following approximateranges which add up to 100 percent by weight.

Weight Percent Active Ingredient Diluent Surfactant Water-Dispersibleand Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and PowdersOil Dispersions, Suspensions,    1-50 40-99    0-50 Emulsions, Solutions(including Emulsifiable Concentrates) Dusts    1-25 70-99    0-5 Granules and Pellets 0.001-99 5-99.999 0-15 High Strength Compositions  90-99 0-10    0-2 

Solid diluents include, for example, clays such as bentonite,montmorillonite, attapulgite and kaolin, gypsum, cellulose, titaniumdioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose),silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodiumcarbonate and bicarbonate, and sodium sulfate. Typical solid diluentsare described in Watkins et al., Handbook of Insecticide Dust Diluentsand Carriers, 2nd Ed., Dorland Books, Caldwell, N.J.

Liquid diluents include, for example, water, N,N-dimethylalkanamides(e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide,N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol,triethylene glycol, propylene glycol, dipropylene glycol, polypropyleneglycol, propylene carbonate, butylene carbonate, paraffins (e.g., whitemineral oils, normal paraffins, isoparaffins), alkylbenzenes,alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin,aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes,alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone,isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamylacetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate,tridecyl acetate and isobornyl acetate, other esters such as alkylatedlactate esters, dibasic esters and γ-butyrolactone, and alcohols, whichcan be linear, branched, saturated or unsaturated, such as methanol,ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol,n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol,isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleylalcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol andbenzyl alcohol. Liquid diluents also include glycerol esters ofsaturated and unsaturated fatty acids (typically C₆-C₂₂), such as plantseed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn(maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean,rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beeftallow, pork tallow, lard, cod liver oil, fish oil), and mixturesthereof. Liquid diluents also include alkylated fatty acids (e.g.,methylated, ethylated, butylated) wherein the fatty acids may beobtained by hydrolysis of glycerol esters from plant and animal sources,and can be purified by distillation. Typical liquid diluents aredescribed in Marsden, Solvents Guide, 2nd Ed., Interscience, New York,1950.

The solid and liquid compositions of the present invention often includeone or more surfactants. Surfactants can be classified as nonionic,anionic or cationic. Nonionic surfactants useful for the presentcompositions include, but are not limited to: alcohol alkoxylates suchas alcohol alkoxylates based on natural and synthetic alcohols (whichmay be branched or linear) and prepared from the alcohols and ethyleneoxide, propylene oxide, butylene oxide or mixtures thereof; amineethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylatedtriglycerides such as ethoxylated soybean, castor and rapeseed oils;alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenolethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates(prepared from the phenols and ethylene oxide, propylene oxide, butyleneoxide or mixtures thereof); block polymers prepared from ethylene oxideor propylene oxide and reverse block polymers where the terminal blocksare prepared from propylene oxide; ethoxylated fatty acids; ethoxylatedfatty esters and oils; ethoxylated methyl esters; ethoxylatedtristyrylphenol (including those prepared from ethylene oxide, propyleneoxide, butylene oxide or mixtures thereof); fatty acid esters, glycerolesters, lanolin-based derivatives, polyethoxylate esters such aspolyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitolfatty acid esters and polyethoxylated glycerol fatty acid esters; othersorbitan derivatives such as sorbitan esters; polymeric surfactants suchas random copolymers, block copolymers, alkyd peg (polyethylene glycol)resins, graft or comb polymers and star polymers; polyethylene glycols(pegs); polyethylene glycol fatty acid esters; silicone-basedsurfactants; and sugar-derivatives such as sucrose esters, alkylpolyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkylarylsulfonic acids and their salts; carboxylated alcohol or alkylphenolethoxylates; diphenyl sulfonate derivatives; lignin and ligninderivatives such as lignosulfonates; maleic or succinic acids or theiranhydrides; olefin sulfonates; phosphate esters such as phosphate estersof alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates andphosphate esters of styryl phenol ethoxylates; protein-basedsurfactants; sarcosine derivatives; styryl phenol ether sulfate;sulfates and sulfonates of oils and fatty acids; sulfates and sulfonatesof ethoxylated alkylphenols; sulfates of alcohols; sulfates ofethoxylated alcohols; sulfonates of amines and amides such asN,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, anddodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes;sulfonates of naphthalene and alkyl naphthalene; sulfonates offractionated petroleum; sulfosuccinamates; and sulfosuccinates and theirderivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides andethoxylated amides; amines such as N-alkyl propanediamines,tripropylenetriamines and dipropylenetetramines, and ethoxylated amines,ethoxylated diamines and propoxylated amines (prepared from the aminesand ethylene oxide, propylene oxide, butylene oxide or mixturesthereof); amine salts such as amine acetates and diamine salts;quaternary ammonium salts such as quaternary salts, ethoxylatedquaternary salts and diquaternary salts; and amine oxides such asalkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

Also useful for the present compositions are mixtures of nonionic andanionic surfactants or mixtures of nonionic and cationic surfactants.Nonionic, anionic and cationic surfactants and their recommended usesare disclosed in a variety of published references includingMcCutcheon's Emulsifiers and Detergents, annual American andInternational Editions published by McCutcheon's Division, TheManufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopediaof Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; andA. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition,John Wiley and Sons, New York, 1987.

Compositions of this invention may also contain formulation auxiliariesand additives, known to those skilled in the art as formulation aids.Such formulation auxiliaries and additives may control: pH (buffers),foaming during processing (antifoams such polyorganosiloxanes (e.g.,Rhodorsil® 416)), sedimentation of active ingredients (suspendingagents), viscosity (thixotropic thickeners), in-container microbialgrowth (antimicrobials), product freezing (antifreezes), color(dyes/pigment dispersions (e.g., Pro-lzed® Colorant Red)), wash-off(film formers or stickers), evaporation (evaporation retardants), andother formulation attributes. Film formers include, for example,polyvinyl acetates, polyvinyl acetate copolymers,polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols,polyvinyl alcohol copolymers and waxes. Examples of formulationauxiliaries and additives include those listed in McCutcheon's Volume 2:Functional Materials, annual International and North American editionspublished by McCutcheon's Division, The Manufacturing ConfectionerPublishing Co.; and PCT Publication WO 03/024222.

Solutions, including emulsifiable concentrates, can be prepared bysimply mixing the ingredients. If the solvent of a liquid compositionintended for use as an emulsifiable concentrate is water-immiscible, anemulsifier is typically added to emulsify the active-containing solventupon dilution with water. Active ingredient slurries, with particlediameters of up to 2,000 μm can be wet milled using media mills toobtain particles with average diameters below 3 μm. Aqueous slurries canbe made into finished suspension concentrates (see, for example, U.S.Pat. No. 3,060,084) or further processed by spray drying to formwater-dispersible granules. Dry formulations usually require dry millingprocesses, which produce average particle diameters in the 2 to 10 μmrange. Dusts and powders can be prepared by blending and, usually,grinding as in a hammer mill or fluid-energy mill. Granules and pelletscan be prepared by spraying the active material upon preformed granularcarriers or by agglomeration techniques. See Browning, “Agglomeration”,Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry's ChemicalEngineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57and following, and WO 91/13546. Pellets can be prepared as described inU.S. Pat. No. 4,172,714. Water-dispersible and water-soluble granulescan be prepared as taught in U.S. Pat. No. 4,144,050, U.S. Pat. Nos.3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S.Pat. No. 5,180,587, U.S. Pat. No. 5,232,701 and U.S. Pat. No. 5,208,030.Films can be prepared as taught in GB 2,095,558 and U.S. Pat. No.3,299,566.

For further information regarding the art of formulation, see T. S.Woods, “The Formulator's Toolbox—Product Forms for Modern Agriculture”in Pesticide Chemistry and Bioscience, The Food-Environment Challenge,T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th InternationalCongress on Pesticide Chemistry, The Royal Society of Chemistry,Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, Col. 6,line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No.3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12,15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182;U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 andExamples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons,Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8thEd., Blackwell Scientific Publications, Oxford, 1989; and Developmentsin formulation technology, PJB Publications, Richmond, UK, 2000.

In the following Examples, all percentages are by weight and allformulations are prepared in conventional ways. Compound numbers referto compounds in Index Tables A-C.

Example A

High Strength Concentrate Compound 1 98.5% silica aerogel 0.5% syntheticamorphous fine silica 1.0%

Example B

Wettable Powder Compound 2 65.0% dodecylphenol polyethylene glycol ether2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0%montmorillonite (calcined) 23.0%

Example C

Granule Compound 4 10.0% attapulgite granules (low volatile matter,0.71/0.30 mm; 90.0% U.S.S. No. 25-50 sieves)

Example D

Extruded Pellet Compound 3 25.0% hydrated attapulgite 3.0% crude calciumligninsulfonate 10.0% sodium dihydrogen phosphate 0.5% water 61.5%

Example E

Extruded Pellet Compound 6 25.0% anhydrous sodium sulfate 10.0% crudecalcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0%calcium/magnesium bentonite 59.0%

Example F

Microemulsion Compound 4 1.0% triacetine 30.0% C₈-C₁₀ alkylpolyglycoside30.0% glyceryl monooleate 19.0% water 20.0%

Example G

Emulsifiable Concentrate Compound 21 10.0% C₈-C₁₀ fatty acid methylester 70.0% polyoxyethylene sorbitol hexoleate 20.0%

The compounds of this invention are useful as plant disease controlagents. The present invention therefore further comprises a method forcontrolling plant diseases caused by fungal plant pathogens comprisingapplying to the plant or portion thereof to be protected, or to theplant seed to be protected, an effective amount of a compound of theinvention or a fungicidal composition containing said compound. Thecompounds and/or compositions of this invention provide control ofdiseases caused by a broad spectrum of fungal plant pathogens in theBasidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They areeffective in controlling a broad spectrum of plant diseases,particularly foliar pathogens of ornamental, turf, vegetable, field,cereal, and fruit crops. These pathogens include: Oomycetes, includingPhytophthora diseases such as Phytophthora infestans, Phytophthoramegasperma, Phytophthora parasitica, Phytophthora cinnamomi andPhytophthora capsici, Pythium diseases such as Pythium aphanidermatum,and diseases in the Peronosporaceae family such as Plasmopara viticola,Peronospora spp. (including Peronospora tabacina and Peronosporaparasitica), Pseudoperonospora spp. (including Pseudoperonosporacubensis) and Bremia lactucae; Ascomycetes, including Alternariadiseases such as Alternaria solani and Alternaria brassicae, Guignardiadiseases such as Guignardia bidwell, Venturia diseases such as Venturiainaequalis, Septoria diseases such as Septoria nodorum and Septoriatritici, powdery mildew diseases such as Erysiphe spp. (includingErysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerothecafuligena and Podosphaera leucotricha, Pseudocercosporellaherpotrichoides, Botrytis diseases such as Botrytis cinerea, Moniliniafructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum,Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases suchas Helminthosporium tritici repentis, Pyrenophora teres, anthracnosediseases such as Glomerella or Colletotrichum spp. (such asColletotrichum graminicola and Colletotrichum orbiculare), andGaeumannomyces graminis; Basidiomycetes, including rust diseases causedby Puccinia spp. (such as Puccinia recondite, Puccinia striiformis,Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileiavastatrix and Phakopsora pachyrhizi; other pathogens includingRhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such asFusarium roseum, Fusarium graminearum and Fusarium oxysporum;Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis;Cercosporidium personatum, Cercospora arachidicola and Cercosporabeticola; and other genera and species closely related to thesepathogens. In addition to their fungicidal activity, the compositions orcombinations also have activity against bacteria such as Erwiniaamylovora, Xanthomonas campestris, Pseudomonas syringae, and otherrelated species. Of note is control provided of disease caused by theAscomycete and Basidiomycete classes.

Plant disease control is ordinarily accomplished by applying aneffective amount of a compound of this invention either pre- orpost-infection, to the portion of the plant to be protected such as theroots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media(soil or sand) in which the plants to be protected are growing. Thecompounds can also be applied to seeds to protect the seeds andseedlings developing from the seeds. The compounds can also be appliedthrough irrigation water to treat plants.

Rates of application for these compounds can be influenced by manyfactors of the environment and should be determined under actual useconditions. Foliage can normally be protected when treated at a rate offrom less than about 1 g/ha to about 5,000 g/ha of active ingredient.Seed and seedlings can normally be protected when seed is treated at arate of from about 0.1 to about 10 g per kilogram of seed.

Compounds of this invention can also be mixed with one or more otherinsecticides, fungicides, nematocides, bactericides, acaricides, growthregulators, chemosterilants, semiochemicals, repellents, attractants,pheromones, feeding stimulants or other biologically active compounds toform a multi-component pesticide giving an even broader spectrum ofagricultural protection. Examples of such agricultural protectants withwhich compounds of this invention can be formulated are: insecticidessuch as abamectin, acephate, acetamiprid, amidoflumet (S-1955),avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate,3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide,buprofezin, carbofuran, cartap, chlorantraniliprole (DPX-E2Y45),chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl,chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin,cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin,diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin,dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, enestroburin(SYP-Z071), esfenvalerate, ethiprole, fenothiocarb, fenoxycarb,fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide,flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron,fonophos, halofenozide, hexaflumuron, hydramethylnon, imidacloprid,indoxacarb, isofenphos, lufenuron, malathion, metaflumizone,metaldehyde, methamidophos, methidathion, methomyl, methoprene,methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram,nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion,parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon,pirimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole,pyrethrin, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen,rotenone, rynaxypyr, ryanodine, spinetoram, spinosad, spirodiclofen,spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide,teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid,thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate,trichlorfon and triflumuron; fungicides such as acibenzolar-S-methyl,aldimorph, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl,benalaxyl-M, benodanil, benomyl, benthiavalicarb,benthiavalicarb-isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol,bixafen, blasticidin-S, Bordeaux mixture (tribasic copper sulfate),boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol,captan, carbendazim, chloroneb, chlorothalonil, chlozolinate,clotrimazole, copper oxychloride, copper salts such as copper sulfateand copper hydroxide, cyazofamid, cyflufenamid, cymoxanil,cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine,dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol,dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap,dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole,ethaboxam, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin acetate, fentin chloride, fentinhydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover,flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin,fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol,folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametpyr,hexaconazole, hymexazol, guazatine, imazalil, imibenconazole,iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb,isoprothiolane, isotianil, kasugamycin, kresoxim-methyl, mancozeb,mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M,metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim,metrafenone, myclobutanil, naftifine, neo-asozin (ferricmethanearsonate), nuarimol, octhilinone, ofurace, orysastrobin,oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline,penconazole, pencycuron, penthiopyrad, pefurazoate, phosphorous acid andsalts, phthalide, picobenzamid, picoxystrobin, piperalin, polyoxin,probenazole, prochloraz, procymidone, propamocarb,propamocarb-hydrochloride, propiconazole, propineb, proquinazid,prothioconazole, pyraclostrobin, pryazophos, pyribencarb, pyrifenox,pyrimethanil, pyrolnitrine, pyroquilon, quinomethionate, quinoxyfen,quintozene, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur,tebuconazole, tecloftalam, tecnazene, terbinafine, tetraconazole,thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram,tiadinil, tolclofos-methyl, tolyfluanid, triadimefon, triadimenol,triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole,trifloxystrobin, triforine, triticonazole, uniconazole, validamycin,valiphenal, vinclozolin, zineb, ziram, zoxamide,5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)[1,2,4]triazolo[1,5-a]pyrimidine (BAS600),N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazol-4-carboxamide,N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide,N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide,2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one,3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine,4-fluorophenylN-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate,N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]-benzeneacetamide,α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]-ethoxy]imino]methyl]benzeneacetamide,N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide,2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile,N-[2-(1S,2R)-[1,1′-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide,and N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide;nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos;bactericides such as streptomycin; acaricides such as amitraz,chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor,etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate,hexythiazox, propargite, pyridaben and tebufenpyrad; and biologicalagents including entomopathogenic bacteria, such as Bacillusthuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki,and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g.,Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardinefungus; and entomopathogenic virus including baculovirus,nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus(GV) such as CpGV.

Compounds of this invention and compositions thereof can be applied toplants genetically transformed to express proteins toxic to invertebratepests (such as Bacillus thuringiensis delta-endotoxins). The effect ofthe exogenously applied fungicidal compounds of this invention may besynergistic with the expressed toxin proteins.

General references for agricultural protectants (i.e., insecticides,fungicides, nematocides, acaricides, herbicides and biological agents)include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed.,British Crop Protection Council, Farnham, Surrey, U. K., 2003 and TheBioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British CropProtection Council, Farnham, Surrey, U. K., 2001.

For embodiments where one or more of these various mixing partners areused, the weight ratio of these various mixing partners (in total) tothe compound of Formula 1 is typically between about 1:100 and about3000:1. Of note are weight ratios between about 1:30 and about 300:1(for example ratios between about 1:1 and about 30:1). It will beevident that including these additional components may expand thespectrum of diseases controlled beyond the spectrum controlled by thecompound of Formula 1 alone.

In one mixture embodiment, granules of a solid composition comprising acompound of Formula 1 is mixed with granules of a solid compositioncomprising another agricultural protectant. These granule mixtures canbe in accordance with the general granule mixture disclosure of PCTPatent Publication WO 94/24861 or more preferably the homogenous granulemixture teaching of U.S. Pat. No. 6,022,552.

Of note are combinations (e.g., in the form of compositions) of (a) acompound of Formula 1 with (b) at least one other fungicide. Ofparticular note are such combinations where the other fungicide hasdifferent site of action from the compound of Formula 1. In certaininstances, combinations with other fungicides having a similar spectrumof control but a different site of action will be particularlyadvantageous for resistance management. Of particular note arecompositions which in addition to a compound of Formula 1 include atleast one compound selected from the group consisting of

-   -   (b1) methyl benzimidazole carbamate (MBC) fungicides;    -   (b2) dicarboximide fungicides;    -   (b3) demethylation inhibitor (DMI) fungicides;    -   (b4) phenylamide fungicides;    -   (b5) amine/morpholine fungicides;    -   (b6) phospholipid biosynthesis inhibitor fungicides;    -   (b7) carboxamide fungicides;    -   (b8) hydroxy(2-amino-)pyrimidine fungicides;    -   (b9) anilinopyrimidine fungicides;    -   (b10) N-phenyl carbamate fungicides;    -   (b11) quinone outside inhibitor (QoI) fungicides;    -   (b12) phenylpyrrole fungicides;    -   (b13) quinoline fungicides;    -   (b14) lipid peroxidation inhibitor fungicides;    -   (b15) melanin biosynthesis inhibitors-reductase (MBI-R)        fungicides;    -   (b16) melanin biosynthesis inhibitors-dehydratase (MBI-D)        fungicides;    -   (b17) hydroxyanilide fungicides;    -   (b18) squalene-epoxidase inhibitor fungicides;    -   (b19) polyoxin fungicides;    -   (b20) phenylurea fungicides;    -   (b21) quinone inside inhibitor (QiI) fungicides;    -   (b22) benzamide fungicides;    -   (b23) enopyranuronic acid antibiotic fungicides;    -   (b24) hexopyranosyl antibiotic fungicides;    -   (b25) glucopyranosyl antibiotic: protein synthesis fungicides;    -   (b26) glucopyranosyl antibiotic: trehalase and inositol        biosynthesis fungicides;    -   (b27) cyanoacetamideoxime fungicides;    -   (b28) carbamate fungicides;    -   (b29) oxidative phosphorylation uncoupling fungicides;    -   (b30) organo tin fungicides;    -   (b31) carboxylic acid fungicides;    -   (b32) heteroaromatic fungicides;    -   (b33) phosphonate fungicides;    -   (b34) phthalamic acid fungicides;    -   (b35) benzotriazine fungicides;    -   (b36) benzene-sulfonamide fungicides;    -   (b37) pyridazinone fungicides;    -   (b38) thiophene-carboxamide fungicides;    -   (b39) pyrimidinamide fungicides;    -   (b40) carboxylic acid amide (CAA) fungicides;    -   (b41) tetracycline antibiotic fungicides;    -   (b42) thiocarbamate fungicides;    -   (b43) benzamide fungicides;    -   (b44) host plant defense induction fungicides;    -   (b45) multi-site contact activity fungicides;    -   (b46) fungicides other than fungicides of components (b1)        through (b45); and salts of compounds of (b1) through (b46).

“Methyl benzimidazole carbamate (MBC) fungicides (b1)” (FungicideResistance Action Committee (FRAC) code 1) inhibit mitosis by binding toβ-tubulin during microtubule assembly. Inhibition of microtubuleassembly can disrupt cell division, transport within the cell and cellstructure. Methyl benzimidazole carbamate fungicides includebenzimidazole and thiophanate fungicides. The benzimidazoles includebenomyl, carbendazim, fuberidazole and thiabendazole. The thiophanatesinclude thiophanate and thiophanate-methyl.

“Dicarboximide fungicides (b2)” (Fungicide Resistance Action Committee(FRAC) code 2) are proposed to inhibit a lipid peroxidation in fungithrough interference with NADH cytochrome c reductase. Examples includechlozolinate, iprodione, procymidone and vinclozolin.

“Demethylation inhibitor (DMI) fungicides (b3)” (Fungicide ResistanceAction Committee (FRAC) code 3) inhibit C14-demethylase which plays arole in sterol production. Sterols, such as ergosterol, are needed formembrane structure and function, making them essential for thedevelopment of functional cell walls. Therefore, exposure to thesefungicides result in abnormal growth and eventually death of sensitivefungi. DMI fungicides are divided between several chemical classes:azoles (including triazoles and imidazoles), pyrimidines, piperazinesand pyridines. The triazoles include azaconazole, bitertanol,bromuconazole, cyproconazole, difenoconazole, diniconazole (includingdiniconazole-M), epoxiconazole, etaconazole, fenbuconazole,fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole,ipconazole, metconazole, myclobutanil, penconazole, propiconazole,prothioconazole, quinconazole, simeconazole, tebuconazole,tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole.The imidazoles include clotrimazole, econazole, imazalil, isoconazole,miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole. Thepyrimidines include fenarimol, nuarimol and triarimol. The piperazinesinclude triforine. The pyridines include buthiobate and pyrifenox.Biochemical investigations have shown that all of the above mentionedfungicides are DMI fungicides as described by K. H. Kuck et al. inModern Selective Fungicides—Properties, Applications and Mechanisms ofAction, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.

“Phenylamide fungicides (b4)” (Fungicide Resistance Action Committee(FRAC) code 4) are specific inhibitors of RNA polymerase in Oomycetefungi. Sensitive fungi exposed to these fungicides show a reducedcapacity to incorporate uridine into rRNA. Growth and development insensitive fungi is prevented by exposure to this class of fungicide.Phenylamide fungicides include acylalanine, oxazolidinone andbutyrolactone fungicides. The acylalanines include benalaxyl,benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M/mefenoxam. Theoxazolidinones include oxadixyl. The butyrolactones include ofurace.

“Amine/morpholine fungicides (b5)” (Fungicide Resistance ActionCommittee (FRAC) code 5) inhibit two target sites within the sterolbiosynthetic pathway, Δ⁸→Δ⁷ isomerase and Δ¹⁴ reductase. Sterols, suchas ergosterol, are needed for membrane structure and function, makingthem essential for the development of functional cell walls. Therefore,exposure to these fungicides results in abnormal growth and eventuallydeath of sensitive fungi. Amine/morpholine fungicides (also known asnon-DMI sterol biosynthesis inhibitors) include morpholine, piperidineand spiroketal-amine fungicides. The morpholines include aldimorph,dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidinesinclude fenpropidin and piperalin. The spiroketal-amines includespiroxamine.

“Phospholipid biosynthesis inhibitor fungicides (b6)” (FungicideResistance Action Committee (FRAC) code 6) inhibit growth of fungi byaffecting phospholipid biosynthesis. Phospholipid biosynthesisfungicides include phosphorothiolate and dithiolane fungicides. Thephosphorothiolates include edifenphos, iprobenfos and pyrazophos. Thedithiolanes include isoprothiolane.

“Carboxamide fungicides (b7)” (Fungicide Resistance Action Committee(FRAC) code 7) inhibit Complex II (succinate dehydrogenase) fungalrespiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle)named succinate dehydrogenase. Inhibiting respiration prevents thefungus from making ATP, and thus inhibits growth and reproduction.Carboxamide fungicides include benzamide, furan carboxamide, oxathiincarboxamide, thiazole carboxamide, pyrazole carboxamide and pyridinecarboxamide. The Benzamides include benodanil, flutolanil and mepronil.The furan carboxamides include fenfuram. The oxathiin carboxamideinclude carboxin and oxycarboxin. The thiazole carboxamides includethifluzamide. The pyrazole carboxamides include furametpyr,penthiopyrad, bixafen,N-[2-(1S,2R)-[1,1′-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamideandN-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide(PCT Patent Publication WO 2003/010149). The pyridine carboxamideinclude boscalid.

“Hydroxy(2-amino-)pyrimidine fungicides (b8)” (Fungicide ResistanceAction Committee (FRAC) code 8) inhibit nucleic acid synthesis byinterfering with adenosine deaminase. Examples include bupirimate,dimethirimol and ethirimol.

“Anilinopyrimidine fungicides (b9)” (Fungicide Resistance ActionCommittee (FRAC) code 9) are proposed to inhibit biosynthesis of theamino acid methionine and to disrupt the secretion of hydrolytic enzymesthat lyse plant cells during infection. Examples include cyprodinil,mepanipyrim and pyrimethanil.

“N-Phenyl carbamate fungicides (b10)” (Fungicide Resistance ActionCommittee (FRAC) code 10) inhibit mitosis by binding to β-tubulin anddisrupting microtubule assembly Inhibition of microtubule assembly candisrupt cell division, transport within the cell and cell structure.Examples include diethofencarb.

“Quinone outside inhibitor (QoI) fungicides (b11)” (Fungicide ResistanceAction Committee (FRAC) code 11) inhibit Complex III mitochondrialrespiration in fungi by affecting ubiquinol oxidase. Oxidation ofubiquinol is blocked at the “quinone outside” (Q_(O)) site of thecytochrome bc₁ complex, which is located in the inner mitochondrialmembrane of fungi. Inhibiting mitochondrial respiration prevents normalfungal growth and development. Quinone outside inhibitor fungicides(also known as strobilurin fungicides) include methoxyacrylate,methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione,dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. Themethoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) andpicoxystrobin. The methoxycarbamates include pyraclostrobin. Theoximinoacetates include kresoxim-methyl and trifloxystrobin. Theoximinoacetamides include dimoxystrobin, metominostrobin, orysastrobinandα-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]-ethoxy]imino]methyl]benzeneacetamide.The oxazolidinediones include famoxadone. The dihydrodioxazines includefluoxastrobin. The imidazolinones include fenamidone. Thebenzylcarbamates include pyribencarb.

“Phenylpyrrole fungicides (b12)” (Fungicide Resistance Action Committee(FRAC) code 12) inhibit a MAP protein kinase associated with osmoticsignal transduction in fungi. Fenpiclonil and fludioxonil are examplesof this fungicide class.

“Quinoline fungicides (b13)” (Fungicide Resistance Action Committee(FRAC) code 13) are proposed to inhibit signal transduction by affectingG-proteins in early cell signaling. They have been shown to interferewith germination and/or appressorium formation in fungi that causepowder mildew diseases. Quinoxyfen is an example of this class offungicide.

“Lipid peroxidation inhibitor fungicides (b14)” (Fungicide ResistanceAction Committee (FRAC) code 14) are proposed to inhibit lipidperoxidation which affects membrane synthesis in fungi. Members of thisclass, such as etridiazole, may also affect other biological processessuch as respiration and melanin biosynthesis. Lipid peroxidationfungicides include aromatic carbon and 1,2,4-thiadiazole fungicides. Thearomatic carbons include biphenyl, chloroneb, dicloran, quintozene,tecnazene and tolclofos-methyl. The 1,2,4-thiadiazoles includeetridiazole.

“Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides (b15)”(Fungicide Resistance Action Committee (FRAC) code 16.1) inhibit thenaphthal reduction step in melanin biosynthesis. Melanin is required forhost plant infection by some fungi. Melanin biosynthesisinhibitors-reductase fungicides include isobenzofuranone,pyrroloquinolinone and triazolobenzothiazole fungicides. Theisobenzofuranones include fthalide. The pyrroloquinolinones includepyroquilon. The triazolobenzothiazoles include tricyclazole.

“Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides (b16)”(Fungicide Resistance Action Committee (FRAC) code 16.2) inhibitscytalone dehydratase in melanin biosynthesis. Melanin in required forhost plant infection by some fungi. Melanin biosynthesisinhibitors-dehydratase fungicides include cyclopropanecarboxamide,carboxamide and propionamide fungicides. The cyclopropanecarboxamidesinclude carpropamid. The carboxamides include diclocymet. Thepropionamides include fenoxanil.

“Hydroxyanilide fungicides (b17)” (Fungicide Resistance Action Committee(FRAC) code 17) inhibit C4-demethylase which plays a role in sterolproduction. Examples include fenhexamid.

“Squalene-epoxidase inhibitor fungicides (b18)” (Fungicide ResistanceAction Committee (FRAC) code 18) inhibit squalene-epoxidase inergosterol biosynthesis pathway. Sterols such as ergosterol are neededfor membrane structure and function making them essential for thedevelopment of functional cell walls. Therefore exposure to thesefungicides result in abnormal growth and eventually death of sensitivefungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate andallylamine fungicides. The thiocarbamates include pyributicarb. Theallylamines include naftifine and terbinafine.

“Polyoxin fungicides (b19)” (Fungicide Resistance Action Committee(FRAC) code 19) inhibit chitin synthase. Examples include polyoxin.

“Phenylurea fungicides (b20)” (Fungicide Resistance Action Committee(FRAC) code 20) are proposed to affect cell division. Examples includepencycuron.

“Quinone inside inhibitor (QiI) fungicides (b21)” (Fungicide ResistanceAction Committee (FRAC) code 21) inhibit Complex III mitochondrialrespiration in fungi by affecting ubiquinol reductase. Reduction ofubiquinol is blocked at the “quinone inside” (Q_(i)) site of thecytochrome bc₁ complex, which is located in the inner mitochondrialmembrane of fungi. Inhibiting mitochondrial respiration prevents normalfungal growth and development. Quinone inside inhibitor fungicidesinclude cyanoimidazole and sulfamoyltriazole fungicides. Thecyanoimidazoles include cyazofamid. The sulfamoyltriazoles includeamisulbrom.

“Benzamide fungicides (b22)” (Fungicide Resistance Action Committee(FRAC) code 22) inhibit mitosis by binding to β-tubulin and disruptingmicrotubule assembly. Inhibition of microtubule assembly can disruptcell division, transport within the cell and cell structure. Examplesinclude zoxamide.

“Enopyranuronic acid antibiotic fungicides (b23)” (Fungicide ResistanceAction Committee (FRAC) code 23) inhibit growth of fungi by affectingprotein biosynthesis. Examples include blasticidin-S.

“Hexopyranosyl antibiotic fungicides (b24)” (Fungicide Resistance ActionCommittee (FRAC) code 24) inhibit growth of fungi by affecting proteinbiosynthesis. Examples include kasugamycin.

“Glucopyranosyl antibiotic: protein synthesis fungicides (b25)”(Fungicide Resistance Action Committee (FRAC) code 25) inhibit growth offungi by affecting protein biosynthesis. Examples include streptomycin.

“Glucopyranosyl antibiotic: trehalase and inositol biosynthesisfungicides (b26)” (Fungicide Resistance Action Committee (FRAC) code 26)inhibit trehalase in inositol biosynthesis pathway. Examples includevalidamycin.

“Cyanoacetamideoxime fungicides (b27)” (Fungicide Resistance ActionCommittee (FRAC) code 27) include cymoxanil.

“Carbamate fungicides (b28)” (Fungicide Resistance Action Committee(FRAC) code 28) are considered multi-site inhibitors of fungal growth.They are proposed to interfere with the synthesis of fatty acids in cellmembranes, which then disrupts cell membrane permeability. propamacarb,propamacarb-hydrochloride, iodocarb, and prothiocarb are examples ofthis fungicide class.

“Oxidative phosphorylation uncoupling fungicides (b29)” (FungicideResistance Action Committee (FRAC) code 29) inhibit fungal respirationby uncoupling oxidative phosphorylation. Inhibiting respiration preventsnormal fungal growth and development. This class includes2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such asferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocapand binapacryl.

“Organo tin fungicides (b30)” (Fungicide Resistance Action Committee(FRAC) code 30) inhibit adenosine triphosphate (ATP) synthase inoxidative phosphorylation pathway. Examples include fentin acetate,fentin chloride and fentin hydroxide.

“Carboxylic acid fungicides (b31)” (Fungicide Resistance ActionCommittee (FRAC) code 31) inhibit growth of fungi by affectingdeoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examplesinclude oxolinic acid.

“Heteroaromatic fungicides (b32)” (Fungicide Resistance Action Committee(FRAC) code 32) are proposed to affect DNA/ribonucleic acid (RNA)synthesis. Heteroaromatic fungicides include isoxazole and isothiazolonefungicides. The isoxazoles include hymexazole and the isothiazolonesinclude octhilinone.

“Phosphonate fungicides (b33)” (Fungicide Resistance Action Committee(FRAC) code 33) include phosphorous acid and its various salts,including fosetyl-aluminum.

“Phthalamic acid fungicides (b34)” (Fungicide Resistance ActionCommittee (FRAC) code 34) include teclofthalam.

“Benzotriazine fungicides (b35)” (Fungicide Resistance Action Committee(FRAC) code 35) include triazoxide.

“Benzene-sulfonamide fungicides (b36)” (Fungicide Resistance ActionCommittee (FRAC) code 36) include flusulfamide.

“Pyridazinone fungicides (b37)” (Fungicide Resistance Action Committee(FRAC) code 37) include diclomezine.

“Thiophene-carboxamide fungicides (b38)” (Fungicide Resistance ActionCommittee (FRAC) code 38) are proposed to affect ATP production.Examples include silthiofam.

“Pyrimidinamide fungicides (b39)” (Fungicide Resistance Action Committee(FRAC) code 39) inhibit growth of fungi by affecting phospholipidbiosynthesis and include diflumetorim.

“Carboxylic acid amide (CAA) fungicides (b40)” (Fungicide ResistanceAction Committee (FRAC) code 40) are proposed to inhibit phospholipidbiosynthesis and cell wall deposition. Inhibition of these processesprevents growth and leads to death of the target fungus. Carboxylic acidamide fungicides include cinnamic acid amide, valinamide carbamate andmandelic acid amide fungicides. The cinnamic acid amides includedimethomorph and flumorph. The valinamide carbamates includebenthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valiphenal.The mandelic acid amides include mandipropamid,N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamideandN-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide.

“Tetracycline antibiotic fungicides (b41)” (Fungicide Resistance ActionCommittee (FRAC) code 41) inhibit growth of fungi by affecting complex 1nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examplesinclude oxytetracycline.

“Thiocarbamate fungicides (b42)” (Fungicide Resistance Action Committee(FRAC) code 42) include methasulfocarb.

“Benzamide fungicides (b43)” (Fungicide Resistance Action Committee(FRAC) code 43) inhibit growth of fungi by delocalization ofspectrin-like proteins. Examples include acylpicolide fungicides such asfluopicolide and fluopyram.

“Host plant defense induction fungicides (b44)” (Fungicide ResistanceAction Committee (FRAC) code P) induce host plant defense mechanisms.Host plant defense induction fungicides include benzo-thiadiazole,benzisothiazole and thiadiazole-carboxamide fungicides. Thebenzo-thiadiazoles include acibenzolar-5-methyl. The benzisothiazolesinclude probenazole. The thiadiazole-carboxamides include tiadinil andisotianil.

“Multi-site contact fungicides (b45)” inhibit fungal growth throughmultiple sites of action and have contact/preventive activity. Thisclass of fungicides includes: “copper fungicides (b45.1) (FungicideResistance Action Committee (FRAC) code M1)”, “sulfur fungicides (b45.2)(Fungicide Resistance Action Committee (FRAC) code M2)”,“dithiocarbamate fungicides (b45.3) (Fungicide Resistance ActionCommittee (FRAC) code M3)”, “phthalimide fungicides (b45.4) (FungicideResistance Action Committee (FRAC) code M4)”, “chloronitrile fungicides(b45.5) (Fungicide Resistance Action Committee (FRAC) code M5)”,“sulfamide fungicides (b45.6) (Fungicide Resistance Action Committee(FRAC) code M6)”, “guanidine fungicides (b45.7) (Fungicide ResistanceAction Committee (FRAC) code M7)” “triazines fungicides (b45.8)(Fungicide Resistance Action Committee (FRAC) code M8)” and “quinonefungicides (b45.9) (Fungicide Resistance Action Committee (FRAC) codeM9)”. “Copper fungicides” are inorganic compounds containing copper,typically in the copper(II) oxidation state; examples include copperoxychloride, copper sulfate and copper hydroxide, including compositionssuch as Bordeaux mixture (tribasic copper sulfate). “Sulfur fungicides”are inorganic chemicals containing rings or chains of sulfur atoms;examples include elemental sulfur. “Dithiocarbamate fungicides” containa dithiocarbamate molecular moiety; examples include mancozeb, metiram,propineb, ferbam, maneb, thiram, zineb and ziram. “Phthalimidefungicides” contain a phthalimide molecular moiety; examples includefolpet, captan and captafol. “Chloronitrile fungicides” contain anaromatic ring substituted with chloro and cyano; examples includechlorothalonil. “Sulfamide fungicides” include dichlofluanid andtolyfluanid. “Guanidine fungicides” include dodine, guazatine,iminoctadine albesilate and iminoctadine triacetate. “Triazinesfungicides” include anilazine. “Quinone fungicides” include dithianon.

“Fungicides other than fungicides of component (a) and components (b1)through (b45); (b46)” include certain fungicides considered to have anunknown mode of action. These include: “thiazole carboxamide fungicide(b46.1) (Fungicide Resistance Action Committee (FRAC) code U5)”,“phenyl-acetamide fungicide (b46.2) (Fungicide Resistance ActionCommittee (FRAC) code U6)”, “quinazolinone fungicide (b46.3) (FungicideResistance Action Committee (FRAC) code U7)” and “benzophenone fungicide(b46.4) (Fungicide Resistance Action Committee (FRAC) code U8)”. Thethiazole carboxamides include ethaboxam. The phenyl-acetamides includecyflufenamid andN-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide.The quinazolinones include proquinazid,6-bromo-3-propyl-2-propyloxy-4(3H)-quinazolinone,6,8-diiodo-3-propyl-2-propyloxy-4-(3H)-quinazolinone,6-chloro-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one,2,3-dibutyl-6-chlorothieno[2,3-d]pyrimidin-4(3H)-one,6-bromo-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one,7-bromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one,6-bromo-2-propoxy-3-propylpyrido[2,3-d]pyrimidin-4(3H)-one,6,7-dibromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one,3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido[2,3-d]pyrimidin-4(3H)-one,2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one,2-ethoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one,6-iodo-2-propoxy-3-propyl-4H-1-benzopyran-4-one,2-(2-butynyloxy)-6-iodo-3-propyl-4H-1-benzopyran-4-one,6-iodo-2-(1-methylbutoxy)-3-propyl-4H-1-benzopyran-4-one,2-(3-butenyloxy)-6-iodo-3-propyl-4H-1-benzopyran-4-one,3-butyl-6-iodo-2-(1-methylethoxy)-4H-1-benzopyran-4-one, and6-iodo-3-propyl-2H-1,3-benzoxazine-2,4(3H)-dione 2-(O-methyloxime). Thebenzophenones include metrafenone. The (b46) group also includes5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)[1,2,4]triazolo[1,5-a]pyrimidine(BAS600), 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine(SYP-Z048), 4-fluorophenylN-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate(XR-539),N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide,2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile(OK-5203) andN-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide (TF-991).

Embodiments of the present invention include:

Embodiment B1

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b1) methyl benzimidazole carbamate fungicides such as benomyl,carbendazim and thiophanate-methyl.

Embodiment B2

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b2) dicarboximide fungicides such as procymidone, iprodione andvinclozolin.

Embodiment B3

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b3) demethylation inhibitor fungicides such as epoxiconazole,fluquinconazole, triadimenol, simeconazole, ipconazole, triforine,cyproconazole, difenoconazole, flusilazole, flutriafol, metconazole,myclobutanil, prochloraz, propiconazole, prothioconazole, tebuconazoleand tetraconazole.

Embodiment B4

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b4) phenylamide fungicides such as mefenoxam, metalaxyl, metalaxyl-M,benalaxyl, benalaxyl-M, furalaxyl, ofurace and oxadixyl.

Embodiment B5

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b5) amine/morpholine fungicides such as aldimorph, dodemorph,fenpropimorph, tridemorph, trimorphamide. fenpropidin, piperalin andspiroxamine.

Embodiment B6

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b6) phospholipid biosynthesis inhibitor fungicides such as edifenphosand isoprothiolane.

Embodiment B7

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b7) carboxamide fungicides such as boscalid, penthiopyrad, bixafen,carboxin and oxycarboxin.

Embodiment B8

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b8) hydroxy(2-amino-)pyrimidine fungicides such as ethirimol.

Embodiment B9

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b9) anilinopyrimidine fungicides such as cyprodinil.

Embodiment B10

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b10) N-phenyl carbamate fungicides such as diethofencarb.

Embodiment B11

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b11) quinone outside inhibitor fungicides such as azoxystrobin,pyraclostrobin, kresoxim-methyl, trifloxystrobin, picoxystrobin,pyribencarb, famoxadone, fenamidone, discostrobin, enestrobin,dimoxystrobin, metominostrobin, orysastrobin and fluoxastrobin.

Embodiment B12

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b12) phenylpyrrole fungicides compound such as fenpiclonil andfludioxonil.

Embodiment B13

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b13) quinoline fungicides such as quinoxyfen.

Embodiment B14

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b14) lipid peroxidation inhibitor fungicides such as chloroneb.

Embodiment B15

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b15) melanin biosynthesis inhibitors-reductase fungicides such aspyroquilon and tricyclazole.

Embodiment B16

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b16) melanin biosynthesis inhibitors-dehydratase fungicides such ascarpropamid.

Embodiment B17

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b17) hydroxyanilide fungicides such as fenhexamid.

Embodiment B18

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b18) squalene-epoxidase inhibitor fungicides such as pyributicarb.

Embodiment B19

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b19) polyoxin fungicides such as polyoxin.

Embodiment B20

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b20) phenylurea fungicides such as pencycuron.

Embodiment B21

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b21) quinone inside inhibitor fungicides such as cyazofamid andamisulbrom.

Embodiment B22

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b22) benzamide fungicides such as zoxamide.

Embodiment B23

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b23) enopyranuronic acid antibiotic fungicides such as blasticidin-S.

Embodiment B24

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b24) hexopyranosyl antibiotic fungicides such as kasugamycin.

Embodiment B25

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b25) glucopyranosyl antibiotic: protein synthesis fungicides such asstreptomycin.

Embodiment B26

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesisfungicides such as validamycin.

Embodiment B27

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b27) cyanoacetylamideoxime fungicides such as cymoxanil.

Embodiment B28

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b28) carbamate fungicides such as propamacarb,propamacarb-hydrochloride, prothiocarb and iodocarb.

Embodiment B29

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b29) oxidative phosphorylation uncoupling fungicides such as fluazinam,binapacryl, ferimzone, meptyldinocap and dinocap.

Embodiment B30

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b30) organo tin fungicides such as fentin acetate.

Embodiment B31

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b31) carboxylic acid fungicides such as oxolinic acid.

Embodiment B32

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b32) heteroaromatic fungicides such as hymexazole.

Embodiment B33

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b33) phosphonate fungicides such as phosphorous acid and its varioussalts, including fosetyl-aluminum.

Embodiment B34

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b34) phthalamic acid fungicides such as teclofthalam.

Embodiment B35

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b35) benzotriazine fungicides such as triazoxide.

Embodiment B36

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b36) benzene-sulfonamide fungicides such as flusulfamide.

Embodiment B37

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b37) pyridazinone fungicides such as diclomezine.

Embodiment B38

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b38) thiophene-carboxamide fungicides such as silthiofam.

Embodiment B39

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b39) pyrimidinamide fungicides such as diflumetorim.

Embodiment B40

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b40) carboxylic acid amide fungicides such as dimethomorph,benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, valiphenal,mandipropamid and flumorph.

Embodiment B41

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b41) tetracycline antibiotic fungicides such as oxytetracycline.

Embodiment B42

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b42) thiocarbamate fungicides such as methasulfocarb.

Embodiment B43

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b43) benzamide fungicides such as fluopicolide and fluopyram.

Embodiment B44

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b44) host plant defense induction fungicides such asacibenzolar-S-methyl.

Embodiment B45

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b45) multi-site contact fungicides such as copper oxychloride, coppersulfate, copper hydroxide, Bordeaux composition (tribasic coppersulfide), elemental sulfur, mancozeb, metiram, propineb, ferbam, maneb,thiram, zineb, ziram, folpet, captan, captafol and chlorothalonil.

Embodiment B46

The composition described in the Summary of the Invention (including butnot limited to composition of Embodiments 1 through 37 and A1 throughA4) wherein component (b) includes at least one compound selected from(b46) fungicides other than fungicides of component (a) and components(b1) through (b45) such as ethaboxam, cyflufenamid, proquinazid,metrafenone,5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)[1,2,4]triazolo[1,5-a]pyrimidine(BAS600), 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one,3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine (SYP-Z048),4-fluorophenylN-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate(XR-539),N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide,N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide,2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile(OK-5203) andN-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide (TF-991).

The following TESTS demonstrate the control efficacy of compounds ofthis invention on specific pathogens. The pathogen control protectionafforded by the compounds is not limited, however, to these species SeeIndex Tables A-C for compound descriptions. See Index Table D for ¹H NMRdata. The following abbreviations are used in the Index Tables A-C whichfollow: Cmpd means Compound, Me is methyl, Et is ethyl, Pr is propyl, Buis butyl, c-Pr is cyclopropyl, i-Pr is isopropyl, c-Pn is cyclopentyl,t-Bu is tertiary-butyl, Ph is phenyl, OMe is methoxy, CN is cyano andNO₂ is nitro. (R) or (S) denotes the absolute chirality of theasymmetric carbon center. The abbreviation “Ex.” stands for “Example”and is followed by a number indicating in which example the compound isprepared.

INDEX TABLE A

Cmpd R¹ G m.p. (° C.) 1 (Ex. 1) CH(CH₃)CH₂OCH₃ 3-Cl—Ph ** 2CH(CH₃)CH₂OCH₃ 3-F—Ph * 3 4-tetrahydropyranyl 3-F—Ph * 4 (Ex. 2)4-tetrahydropyranyl 3-Cl—Ph ** 5 (S)—CH(CH₃)CH₂OCH₃ 3-F—Ph * 6C(CH₃)₂CH₂OCH₃ 3-F—Ph * 7 CH(CH₃)CH₂OH 3-F—Ph * 8 CH(CH₃)CH₂OC(═O)CH₃3-F—Ph * 9 c-Pr 3-F—Ph * 10 t-Bu 3-F—Ph * 11 (S)—CH(CH₃)CH₂OCH₃3-Br—Ph * 12 (S)—CH(CH₃)CH₂OCH₃ 3-I—Ph * 13 (S)—CH(CH₃)CH₂OCH₃ 4-F—Ph *14 (S)—CH(CH₃)CH₂OCH₃ 3,4-di-Cl—Ph * 15 (S)—CH(CH₃)CH₂OCH₃ 4-Cl—Ph * 16(S)—CH(CH₃)CH₂OCH₃ 3-Cl—Ph * 17 (S)—CH(CH₃)CH₂OCH₃ 2-F—Ph * 18(S)—CH(CH₃)CH₂OCH₃ 3-CN—Ph * 19 (S)—CH(CH₃)CH₂OCH₃ 3-Me—Ph * 20(S)—CH(CH₃)CH₂OCH₃ 4-Me—Ph * 21 (S)—CH(CH₃)CH₂OCH₃ 3-NO₂—Ph * 22(S)—CH(CH₃)CH₂OCH₃ 3,5-di-F—Ph * 23 (S)—CH(CH₃)CH₂OCH₃ 3-Cl-4-F—Ph * 24(S)—CH(CH₃)CH₂OCH₃ 3,4-di-Me—Ph * 25 (S)—CH(CH₃)CH₂OCH₃ 3-F-4-Me—Ph * 26(S)—CH(CH₃)CH₂OCH₃ 4-Me-3-NO₂—Ph * 27 (S)—CH(CH₃)CH₂OCH₃2-Cl-4-pyridinyl * 28 (S)—CH(CH₃)CH₂OCH₃ 3,5-di-Cl—Ph * 29(S)—CH(CH₃)CH₂OCH₃ 3,4-di-F—Ph * 30 C(CH₃)₂CH₂OCH₃ 3,5-di-F—Ph * 31(S)—CH(CH₃)CH₂OCH₃ 2-F-4-pyridinyl * 32 C(CH₃)₂OCH₃ 3,5-di-F—Ph * 33t-Bu 3,5-di-F—Ph * 34 4-tetrahydropyranyl 3,5-di-F—Ph * 35(S)—CH(CH₃)CH₂OCH₃ 5-F-3-pyridinyl * 36 (S)—CH(CH₃)CH₂OCH₃ 3-CN-5-F—Ph *37 (Ex. 3) (S)—CH(CH₃)CH₂OCH₃ 2-CN-5-pyridinyl ** 38 (S)—CH(CH₃)CH₂OCH₃2-Cl-pyridinyl * 39 (Ex. 4) (S)—CH(CH₃)CH₂OCH₃ 3-F-5-NO₂—Ph ** * SeeIndex Table D for ¹H NMR data. ** See synthesis example for ¹H NMR data.

INDEX TABLE B

Cmpd R¹ G m.p. (° C.)  40 CH(CH₃)CH₂OCH₃ 3-Cl—Ph *  41 CH(CH₃)CH₂OCH₃3-F—Ph *  42 CH(CH₃)CH₂OCH₃ 3-CN—Ph *  43 CH(CH₃)CH₂OCH₃ Ph *  44CH(CH₃)CH₂OCH₃ 3-NO₂—Ph *  45 t-Bu 3-F—Ph *  46 CH(CH₃)CH₂OCH₃2-F-3-Cl—Ph *  47 CH(CH₃)CH₂OCH₃ 2,4-di-F—Ph *  48 CH(CH₃)CH₂OH 3-F—Ph * 49 CH(CH₃)CH₂OCH₃ 2,6-di-F—Ph *  50 CH(CH₃)CH₂OCH₃ 4-F—Ph *  51CH(CH₃)CH₂OCH₃ 3-Me—Ph *  52 CH(CH₃)CH₂OCH₃ 3-MeOC(═O)—Ph *  53CH(CH₃)CH₂OCH₃ 2-F—Ph *  54 CH(CH₃)CH₂OCH₃ 2-Cl-4-pyridinyl *  55CH₂CH₂SCH₃ 3-F—Ph *  56 (S)—CH(CH₃)CH₂OCH₃ 3-F—Ph *  57 (R)—CH(CH₃)CH₂OH3-F—Ph *  58 CH₂CH₂OCH₃ 3-F—Ph *  59 CH(CH₃)CH₂CH₂CH₃ 3-F—Ph *  60 i-Pr3-F—Ph *  61 Et 3-F—Ph *  62 (Ex. 9) c-Pn 3-F—Ph **  63 CH(CH₃)CH₂OCH₃4-CN—Ph *  64 CH₂CH₂CH₂OCH₃ 3-F—Ph *  65 c-Pr 3-F—Ph *  66 NHCH₂CH₃3-F—Ph *  67 (Ex. 10) 4-tetrahydropyranyl 3-F—Ph **  68(R)—CH(CH₃)CH₂OCH₃ 3-F—Ph *  69 (Ex. 11) 4-tetrahydropyranyl 3-Cl—Ph ** 70 CH(CH₃)CH₂OCH₃ 2,3,6-tri-F—Ph *  71 (S)-3-tetrahydrofuranyl 3-F—Ph * 72 (S)-3-tetrahydrofuranyl 3-Cl—Ph *  73 4-tetrahydropyranyl2,3,6-tri-F—Ph *  74 3-tetrahydrofuranyl 3-F—Ph *  753-tetrahydropyranyl 3-F—Ph *  76 (Ex. 6) CH(CH₃)CH₂OCH₃ 2-Cl-6-Me—Ph ** 77 CH(CH₃)CH₂OCH₃ 2,6-di-Me—Ph *  78 CH(CH₃)CH₂OCH₃ 2,6,-di-Cl—Ph *  79CH(CH₃)CH₂OCH₃ 2-Cl-6-F—Ph *  80 4-tetrahydropyranyl 2-Cl-6-Me—Ph *  814-tetrahydropyranyl 2,6-di-Cl—Ph *  82 (Ex. 15)tetrahydrofuran-3-yl-methyl 3-F—Ph **  83 (Ex. 16)tetrahydrofuran-2-yl-methyl 3-F—Ph **  84 (Ex. 18) CH(CH₃)CH₂CH₂OCH₃3-F—Ph **  85 CH(CH₃)CH₂OCH₃ 2-MeO-6-Me—Ph *  86 CH(CH₃)CH₂OCH₃2-Me-1-naphthalenyl *  87 CH(CH₃)CH₂OCH₃ 2-Cl-4,6-di-Me—Ph *  884-tetrahydropyranyl 2-MeO-6-Me—Ph *  89 4-tetrahydropyranyl2-Me-1-naphthalenyl *  90 4-tetrahydropyranyl 2-Cl-4,6-di-Me—Ph *  91CH(CH₃)CH₂OCH₃ 2-Me-5-F—Ph *  92 CH(CH₃)CH₂OCH₃ 5-Cl-2,6-di-Me—Ph *  93CH(CH₃)CH₂OCH₃ 2,4-di-Cl-6-Me—Ph *  94 (Ex. 7) CH(CH₃)CH₂SCH₃ 3-F—Ph ** 95 (Ex. 8) CH(CH₃)CH₂SCH₃ 3-Cl—Ph **  96 (Ex. 17) CH₂CH(CH₃)OCH₃ 3-F—Ph**  97 CH(CH₃)CH₂OCH₃ 2-Cl-6-CF₃—Ph *  98 4-tetrahydropyranyl2-Cl-6-CF₃—Ph *  99 4-tetrahydropyranyl 2,4,6-tri-Cl—Ph * 1004-tetrahydropyranyl 2,4,-di-Cl-6-Me—Ph * 101 (Ex. 12)4-tetrahydropyranyl 2-Cl—Ph ** 102 (Ex. 14) 4-tetrahydropyranyl2-Cl-4-Me—Ph ** 103 (Ex. 13) 4-tetrahydropyranyl 2-Me-4-Cl—Ph ** * SeeIndex Table D for ¹H NMR data. ** See synthesis example for ¹H NMR data.

INDEX TABLE C

Cmpd X Y W Z R¹ G m.p. (° C.) 104 (Ex. 5)  N N N CH 4-tetrahydropyranyl2-Cl-6-Me—Ph ** 105 (Ex. 19) CH N N CH CH(CH₃)CH₂OCH₃ 3-Cl—Ph ** 106(Ex. 20) CH N N CH CH(CH₃)CH₂OCH₃ 3-F—Ph ** 107 (Ex. 21) CH N N CHCH(CH₃)CH₂OCH₃ 3-NO₂—Ph ** 108 (Ex. 22) CH N N CH CH(CH₃)CH₂OCH₃ Ph **109 (Ex. 24) N CH CH N CH(CH₃)CH₂OCH₃ 3-F—Ph ** 110 (Ex. 23) CH N N CHCH(CH₃)CH₂OCH₃ 2-Cl-6-Me—Ph ** ** See synthesis example for ¹H NMR data.

INDEX TABLE D Cmpd ¹H NMR data (CDCl₃ solution unless indicatedotherwise)^(a) 2 δ 8.97 (s, 1H), 8.54 (d, 1H), 8.15 (br s, 1H), 7.71 (brs, 1H), 7.54 (d, 1H), 7.30 (m, 2H), 6.84 (m, 1H), 5.85 (br s, 1H), 4.36(br s, 1H), 3.48 (m, 2H), 3.37 (s, 3H), 1.30 (d, 3H). 3 δ 8.94 (s, 1H),8.56 (d, 1H), 7.75 (br s, 2H), 7.58 (d, 1H), 7.33 (m, 1H), 7.23 (m, 1H),6.85 (m, 1H), 5.47 (br s, 1H), 4.16 (br s, 1H), 4.00 (m, 2H), 3.57 (m,2H), 2.05 (m, 2H), 1.59 (m, 2H). 5 δ 8.97 (s, 1H), 8.54 (d, 1H), 8.15(br s, 1H), 7.71 (br s, 1H), 7.54 (d, 1H), 7.30 (m, 2H), 6.84 (m, 1H),5.85 (br s, 1H), 4.36 (br s, 1H), 3.48 (m, 2H), 3.37 (s, 3H), 1.30 (d,3H). 6 δ 8.92 (s, 1H), 8.56 (d, 1H), 7.81 (br s, 1H), 7.71 (br s, 1H),7.55 (d, 1H), 7.35 (m, 2H), 6.85 (m, 1H), 5.78 (s, 1H), 3.52 (s, 2H),3.36 (s, 3H), 1.48 (s, 6H). 7 δ 8.90 (s, 1H), 8.53 (d, 1H), 8.25 (br s,1H), 7.69 (br s, 1H), 7.62 (s, 1H), 7.30 (m, 2H), 6.83 (m, 1H), 5.64 (brs, 1H0, 3.80 (m, 1H), 3.71 (br s, 1H), 3.50 (m, 2H), 1.23 (d, 3H). 8 δ8.93 (s, 1H), 8.55 (d, 1H), 7.88 (br s, 1H), 7.72 (br s, 1H), 7.60 (d,1H), 7.30 (m, 2H), 6.86 (t, 1H), 5.58 (br s, 1H), 4.50 (br s, 1H), 4.20(s, 2H), 2.06 (s, 3H), 1.30 (d, 3H) 9 δ 8.94 (s, 1H), 8.56 (d, 1H), 7.75(br s, 2H), 7.58 (d, 1H), 7.32 (m, 1H), 7.25 (m, 1H), 6.87 (t, 1H), 5.46(br s, 1H), 4.16 (br s, 1H), 4.00 (m, 1H), 3.57 (m, 1H), 2.07 (m, 1H),1.59 (m, 1H) 10 δ 8.92 (s, 1H), 8.53 (d, 1H), 7.83 (br s, 1H), 7.20 (brs, 1H), 7.54 (d, 1H), 7.32 (m, 2H), 6.86 (t, 1H), 5.56 (br s, 1H), 1.48(s, 9H). 11 δ 8.96 (s, 1H), 8.54 (d, 1H), 8.10 (br s, 1H), 8.01 (br s,1H), 7.54 (d, 1H), 7.48 (br s, 1H) 7.23 (m, 2H), 5.85 (br s, 1H), 4.35(br s, 1H), 3.45 (m, 2H), 3.37 (s, 3H), 1.28 (d, 3H). 12 δ 8.96 (s, 1H),8.54 (d, 1H), 8.16 (br s, 2H), 7.54 (d, 2H), 7.45 (d, 1H) 7.07 (t, 1H),5.88 (br s, 1H), 4.35 (br s, 1H), 3.46 (m, 2H), 3.37 (s, 3H), 1.28 (d,3H). 13 δ 8.89 (s, 1H), 8.52 (d, 1H), 8.38 (br s, 1H), 8.03 (br s, 1H),7.57 (d, 2H), 7.06 (t, 2H), 5.85 (br s, 1H), 4.34 (br s, 1H), 3.47 (m,2H), 3.36 (s, 3H), 1.28 (d, 3H). 14 δ 8.98 (s, 1H), 8.54 (d, 1H), 8.11(br s, 1H), 7.99 (s, 1H), 7.55 (d, 1H), 7.42 (m, 2H), 5.81 (br s, 1H),4.36 (br s, 1H), 3.47 (m, 2H), 3.37 (s, 3H), 1.28 (d, 3H). 15 δ 8.93 (s,1H), 8.53 (d, 1H), 7.94 (br s, 1H), 7.60 (br s, 2H), 7.52 (d, 2H), 7.36(m, 2H), 5.78 (br s, 1H), 4.34 (br s, 1H), 3.47 (m, 2H), 3.36 (s, 3H),1.28 (d, 3H). 16 δ 8.96 (s, 1H), 8.53 (d, 1H), 8.11 (br s, 1H), 7.87 (brs, 1H), 7.55 (d, 1H), 7.45 (d, 1H), 7.27 (t, 1H), 7.11 (d, 1H), 5.83 (brs, 1H), 4.36 (br s, 1H), 3.47 (m, 2H), 3.37 (s, 3H), 1.28 (d, 3H). 17 δ8.94 (s, 1H), 8.54d, 1H), 8.38 (br s, 1H), 7.90 (br s, 1H), 7.23 (m,1H), 7.13 (m, 2H), 5.75 (br s, 1H), 4.35 (br s, 1H), 3.48 (m, 2H), 3.36(s, 3H), 1.28 (d, 3H). 18 δ 9.00 (s, 1H), 8.55 (d, 1H), 8.25 (br s, 2H),7.79 (br s, 1H), 7.55 (d, 1H), 7.45 (m, 2H), 5.82 (br s, 1H), 4.36 (brs, 1H), 3.49 (m, 2H), 3.38 (s, 3H), 1.28 (d, 3H). 19 δ 8.90 (s, 1H),8.53 (d, 1H), 7.77 (br s, 1H), 7.56 (br s, 2H), 7.43 (br s, 1H), 7.41(s, 1H), 7.27 (m, 1H), 6.99 (d, 1H), 5.74 (br s, 1H), 4.35 (br s, 1H),3.48 (m, 2H), 3.38 (s, 3H), 2.39 (s, 3H), 1.28 (d, 3H). 20 δ 8.88 (s,1H), 8.52 (d, 1H), 7.97 (br s, 1H), 7.53 (br s, 1H), 7.48 (br s, 2H),7.18 (m, 2H), 5.81 (br s, 1H), 4.35 (br s, 1H), 3.48 (m, 2H), 3.36 (s,3H), 2.31 (s, 3H), 1.28 (d, 3H). 21 δ 9.02 (s, 1H), 8.05 (br s, 1H),8.56 (d, 1H), 8.44 (br s, 1H), 7.98 (dd, 1H), 7.84 (br s, 1H), 7.60 (s,1H), 7.52 (t, 1H), 5.84 (br s, 1H), 4.36 (br s, 1H), 3.48 (m, 2H), 3.38(s, 3H), 1.29 (d, 3H). 22 δ 8.98 (s, 1H), 8.56 (d, 1H), 7.79 (s, 1H),7.57 (d, 1H), 7.35 (br s, 2H), 6.60 (m, 1H), 5.74 (br s, 1H), 4.37 (brs, 1H), 3.47 (m, 2H), 3.36 (s, 3H), 1.29 (d, 3H). 23 δ 8.98 (s, 1H),8.56 (d, 1H), 7.80 (s, 1H), 7.57 (br s, 1H), 7.55 (d, 2H), 7.47 (s, 1H),6.87 (dt, 1H), 5.74 (br s, 1H), 4.35 (br s, 1H), 3.47 (m, 2H), 3.36 (s,3H), 1.29 (d, 3H). 24 δ 8.87 (s, 1H), 8.54 (d, 1H), 7.87 (s, 1H), 7.55(d, 1H), 7.45 (br s, 1H), 7.34 (s, 1H), 7.15 (d, 1H), 5.95 (br s, 1H),4.35 (br s, 1H), 3.47 (m, 2H), 3.36 (s, 3H), 1.29 (d, 3H). 25 δ 8.93 (s,1H), 8.54 (d, 1H), 7.87 (br s, 1H), 7.61 (br s, 1H), 7.55 (d, 1H), 7.14(m, 2H), 5.79 (br s, 1H), 4.35 (br s, 1H), 3.47 (m, 2H), 3.36 (s, 3H),1.29 (d, 3H). 26 δ 8.98 (s, 1H), 8.84 (br s, 1H), 8.54 (d, 1H), 8.31 (brs, 1H), 7.66 (br s, 1H), 7.55 (d, 1H), 7.31 (d, 1H), 5.84 (br s, 1H),4.35 (br s, 1H), 3.47 (m, 2H), 3.36 (s, 3H), 1.29 (d, 3H). 27 δ 9.07 (s,1H), 8.64 (br s, 1H), 8.57 (d, 1H), 8.32 (d, 1H), 7.99 (br s, 1H), 7.57(d, 1H), 7.54 (d, 1H), 5.80 (d, 1H), 4.39 (br s, 1H), 3.49 (m, 2H), 3.36(s, 3H), 1.31 (d, 3H). 28 δ 8.99 (s, 1H), 8.57 (d, 1H), 8.05 (br s, 1H),7.67 (br s, 2H), 7.54 (d, 1H), 7.31 (s, 1H), 5.78 (br s, 1H), 4.36 (brs, 1H), 3.47 (m, 2H), 3.36 (s, 3H), 1.29 (d, 3H). 29 δ 8.94 (s, 1H),8.55 (d, 1H), 7.77 (br s, 2H), 7.55 (d, 1H), 7.15 (m, 2H), 5.73 (br s,1H), 4.36 (br s, 1H), 3.48 (m, 2H), 3.37 (s, 3H), 1.29 (d, 3H). 30 δ8.95 (s, 1H), 8.52 (d, 1H), 7.79 (br s, 1H), 7.54 (d, 1H), 7.36 (br s,2H), 6.60 (m, 1H), 5.82 (s, 1H), 3.52 (s, 2H), 3.36 (s, 3H), 1.48 (d,6H). 31 δ 9.07 (s, 1H), 8.57 (d, 1H), 8.41 (s, 1H), 8.16 (d, 1H), 7.70(br s, 1H), 7.58 (d, 1H), 7.36 (d, 2H), 6.98 (s, 1H), 5.78 (d, 1H), 4.39(br s, 1H), 3.49 (m, 2H), 3.39 (s, 3H), 1.30 (d, 3H). 32 δ 8.96 (s, 1H),8.56 (d, 1H), 8.14 (s, 1H), 7.57 (d, 1H), 7.36 (br s, 2H), 6.60 (t, 1H),5.70 (br s, 1H), 4.26 (br s, 1H), 3.37 (s, 3H), 1.23 (s, 6H). 33 δ 8.95(s, 1H), 8.54 (d, 1H), 7.69 (br s, 1H), 7.54 (d, 1H), 7.33 (d, 2H), 6.59(t, 1H), 5.54 (s, 1H), 1.49 (s, 9H). 34 δ 8.96 (s, 1H), 8.57 (d, 1H),7.71 (s, 1H), 7.60 (d, 1H), 7.35 (br s, 2H), 6.60 (t, 1H), 5.45 (br s,1H), 4.16 (br s, 1H), 4.00 (m, 2H), 3.57 (m, 2H), 2.05 (m, 2H), 1.59 (m,2H) 35 δ 9.08 (s, 1H), 8.56 (d, 1H), 8.37 (br s, 3H), 8.29 (s, 1H), 7.56(d, 1H), 5.84 (s, 1H), 4.38 (s, 1H), 3.50 (d, 2H), 3.39 (s, 3H), 1.30(d, 3H). 36 δ 9.00 (s, 1H), 8.57 (d, 1H), 7.88 (br s, 1H), 7.82 (s, 1H),7.70 (s, 1H), 7.58 (d, 1H), 7.14 (d, 1H), 5.70 (s, 1H), 4.37 (s, 1H),3.49 (d, 2H), 3.38 (s, 3H), 1.30 (d, 3H). 38 δ 9.00 (s, 1H), 8.68 (s,1H), 8.54 (d, 1H), 8.22 (s, 1H), 8.14 (s, 1H), 7.54 (s, 1H), 7.38 (d,1H), 5.86 (s, 1H), 4.36 (m, 1H), 3.49 (m, 2H), 3.39 (s, 3H), 1.30 (d,3H). 40 δ 8.4 (d, 1H), 8.3 (d, 1H), 7.58 (s, 1H), 7.5 (s, 1H), 7.3 (d,1H), ), 7.2 (1H), 7.0 (m, 1H), 6.9 (d, 1H), 6.6 (s, 1H), 5.4 (d, 1H),4.3 (m, 1H), 3.48 (d, 2H), 3.89 (s, 3H), 1.3 (d, 3H). 41 δ 8.39 (d, 1H),8.34 (d, 1H), 7.53 (s, 1H), 7.33 (d, 1H), 7.24 (m, 2H), 7.10 (d, 1H),6.92 (d, 1H), 6.82 (s, 1H), 6.71 (t, 1H), 5.42 (d, 1H), 4.34 (m, 1H),3.48 (d, 2H), 3.39 (s, 3H), 1.30 (d, 3H). 42 (DMSO-d₆) δ 9.67 (s, 1H),8.44 (d, 1H), 8.35 (m, 2H), 7.88 (d, 1H), 7.55 (s, 1H), 7.48 (t, 1H),7.41 (d, 1H), 7.32 (d, 1H), 7.11 (d, 2H), 4.31 (br s, 1H), 3.47 (m, 1H),3.32 (m, 1H), 3.28 (s, 3H), 1.19 (d, 3H). 43 δ 8.36 (d, 1H), 8.28 (d,1H), 7.54 (s, 1H), 7.36 (d, 5H), 7.24 (m, 1H), 7.06 (d, 1H), 6.88 (d,1H), 6.71 (t, 1H), 5.42 (d, 1H), 4.30 (m, 1H), 3.47 (d, 2H), 3.36 (s,3H), 1.28 (d, 3H). 44 (acetone-d₆) δ 8.96 (m, 2H), 8.42 (m, 2H), 8.06(d, 1H), 7.77 (d, 1H), 7.64 (s, 1H), 7.55 (t, 1H), 7.49 (d, 1H), 7.13(d, 1H), 6.18 (br s, 1H), 4.38 (m, 1H), 3.55 (m, 1H), 3.44 (m, 1H), 3.35(s, 3H), 1.29 (d, 3H). 45 δ 8.33 (m, 2H), 7.64 (s, 1H), 7.48 (s, 1H),7.28 (, 3H), 7.09 (m, 1H) 6.89 (d, 1H), 6.73 (t, 1H), 5.43 (s, 1H), 1.48(s, 9H). 46 δ 8.39 (d, 1H), 8.34 (d, 1H), 8.07 (t, 1H), 7.47 (s, 1H),7.32 (d, 1H), 7.04 (m, 3H), 6.93 (d, 1H), 5.57 (d, 1H), 4.33 (m, 1H),3.48 (d, 2H), 3.39 (s, 3H), 1.30 (d, 3H) 47 8.38 (d, 1H), 8.29 (d, 1H),7.98 (m, 1H), 7.35 (s, 1H), 7.27 (d, 1H), 6.91 (m, 4H), 5.57 (d, 1H),4.35 (m, 1H), 3.48 (d, 2H), 3.39 (s, 3H), 1.30 (d, 3H). 48 δ 8.33 (d,1H), 8.29 (d, 1H), 7.45 (s, 2H), 7.35 (d, 1H), 7.20 (m, 2H), 7.08 (d,1H), 6.71 (t, 1H), 5.63 (d, 1H), 4.22 (m, 1H), 3.76 (d, 1H), 3.65 (m,1H), 1.25 (d, 3H). 49 δ 8.36 (d, 1H), 8.28 (d, 1H), 7.32 (d, 1H), 7.14(m, 2H), 7.03 (t, 2H), 6.90 (d, 1H), 6.61 (s, 1H), 5.46 (d, 1H), 4.30(m, 1H), 3.47 (d, 2H), 3.36 (s, 3H), 1.28 (d, 3H). 50 δ 8.35 (d, 1H),8.27 (d, 1H), 7.36 (d, 3H), 7.24 (m, 1H), 7.05 (d, 2H), 6.92 (s, 1H),6.88 (d, 1H), 5.42 (d, 1H), 4.30 (m, 1H), 3.47 (d, 2H), 3.36 (s, 3H),1.28 (d, 3H). 51 δ 8.35 (d, 1H), 8.29 (d, 1H), 7.52 (s, 1H), 7.20 (m,4H), 6.89 (d, 1H), 6.88 (s, 1H), 6.80 (s, 1H), 5.45 (d, 1H), 4.30 (m,1H), 3.47 (d, 2H), 3.36 (s, 3H), 1.28 (d, 3H). 52 δ 8.38 (d, 1H), 8.35(d, 1H), 8.05 (s, 1H), 7.73 (d, 2H), 7.49 (s, 1H), 7.42 (t, 1H), 7.31(d, 1H), 6.93 (d, 1H), 6.76 (s, 1H), 5.39 (d, 1H), 4.30 (m, 1H), 3.47(d, 2H), 3.36 (s, 3H), 1.28 (d, 3H). 53 δ 8.37 (d, 1H), 8.33 (d, 1H),8.09 (t, 1H), 7.46 (s, 1H), 7.30 (t, 1H), 7.14 (m, 2H), 6.99 (m, 1H),6.93 (d, 1H), 6.85 (s, 1H), 5.49 (d, 1H), 4.30 (m, 1H), 3.47 (d, 2H),3.36 (s, 3H), 1.28 (d, 3H). 54 δ 8.42 (d, 1H), 8.36 (d, 1H), 8.11 (d,1H), 7.73 (d, 1H), 7.49 (s, 1H), 7.49 (s, 1H), 7.41 (d, 1H), 7.23 (d,1H), 6.86 (d, 1H), 6.73 (d, 1H), 5.49 (d, 1H), 4.35 (m, 1H), 3.47 (d,2H), 3.38 (s, 3H), 1.30 (d, 3H). 55 δ 8.41 (d, 1H), 8.35 (d, 1H), 7.52(s, 1H), 7.36 (m, 1H), 7.30 (m, 1H), 7.25 (m, 1H), 7.08 (d, 1H), 6.97(d, 1H), 6.78 (s, 1H), 6.72 (t, 1H), 5.63 (m, 1H), 3.73 (m, 2H), 2.81(t, 2H), 2.15 (s, 3H) 56 δ 8.39 (d, 1H), 8.34 (d, 1H), 7.53 (s, 1H),7.33 (d, 1H), 7.24 (m, 2H), 7.10 (d, 1H), 6.92 (d, 1H), 6.82 (s, 1H),6.71 (t, 1H), 5.42 (d, 1H), 4.34 (m, 1H), 3.48 (d, 2H), 3.39 (s, 3H),1.30 (d, 3H). 57 (DMSO-d₆) δ 9.54 (s, 1H), 8.43 (d, 1H), 8.34 (d, 2H),7.89 (d, 1H), 7.54 (s, 1H), 7.38 (m, 2H), 7.30 (m, 1H), 7.11 (d, 2H),6.96 (t, 1H), 4.75 (d, 1H), 3.86 (m, 1H), 3.34 (m 1H) 1.10 (d, 3H). 58 δ8.39 (d, 1H), 8.33 (d, 1H), 7.53 (s, 1H), 7.28 (m, 4H), 7.09 (d, 1H),6.93 (d, 1H), 6.72 (t, 1H), 5.81 (br s, 1H), 3.69 (m, 2H), 3.60 (m, 2H),3.39 (s, 3H). 59 δ 8.37 (d, 1H), 8.33 (d, 1H), 7.56 (s, 1H), 7.28 (m,4H), 7.07 (d, 1H), 6.89 (d, 1H), 6.73 (t, 1H), 5.28 (br s, 1H), 4.15 (m,1H), 3.69 (m, 2H), 1.53 (m, 2H), 1.42 (m, 2H), 1.22 (d, 3H), 0.91 (t,3H). 60 δ 8.38 (d, 1H), 8.33 (d, 1H), 7.56 (s, 1H), 7.28 (m, 3H), 7.07(d, 1H), 7.03 (s, 1H), 6.91 (d, 1H), 6.73 (t, 1H), 5.20 (br s, 1H), 4.23(m, 1H), 1.29 (d, 6H). 61 (acetone-d₆) δ 8.68 (s, 1H), 8.40 (d, 1H),8.36 (d, 1H), 7.96 (d, 1H), 7.62 (s, 1H), 7.43 (d, 1H), 7.36 (d, 1H),7.27 (m 1H), 7.10 (d, 1H), 6.67 (t, 1H), 6.43 (s, 1H), 3.52 (m, 2H),1.25 (t, 3H). 63 δ 8.38 (m, 2H), 7.68 (s, 1H), 7.60 (m, 5H), 7.37 (d,1H), 6.93 (d, 1H), 5.67 (d, 1H), 4.36 (m, 1H), 3.48 (m, 2H), 3.38 (s,3H), 1.31 (d, 3H) 64 δ 8.37 (d, 1H), 8.32 (d, 1H), 7.56 (s, 1H), 7.47(s, 1H), 7.28 (m, 3H), 7.09 (d, 1H), 6.89 (d, 1H), 6.71 (t, 1H), 5.91(br s, 1H), 3.59 (m, 2H), 3.49 (t, 2H), 3.34 (s, 3H), 1.91 (m, 2H). 65(DMSO-d₆) δ 9.57 (s, 1H), 8.46 (s, 1H), 8.34 (d, 1H), 8.13 (s, 1H), 7.85(d, 1H), 7.57 (s, 1H), 7.52 (s, 1H), 7.40 (m 2H), 7.30 (m, 2H), 7.15 (d,1H), 6.71 (m, 1H), 2.82 (br s, 1H), 0.70 (m, 2H), 0.53 (s, 2H). 66 δ8.39 (d, 1H), 8.33 (d, 1H), 7.54 (s, 1H), 7.31 (m, 3H), 7.09 (d, 1H),6.92 (d, 1H), 6.90 (s, 1H), 6.73 (t, 1H), 5.28 (br s, 1H), 3.54 (m, 2H),1.28 (t, 3H). 68 δ 8.39 (d, 1H), 8.33 (d, 1H), 7.54 (s, 1H), 7.39 (s,1H), 7.33 (m, 3H), 7.09 (d, 1H), 6.90 (d, 1H), 6.73 (t, 1H), 5.67 (br s,1H), 4.34 (m 1H), 3.48 (m, 2H), 3.37 (s, 3H), 1.29 (d, 3H). 70 δ 8.36(d, 1H), 8.30 (d, 1H), 7.35 (d, 1H), 7.22 (s, 1H), 7.00 (m, 2H), 6.91(d, 1H), 6.81 (s, 1H), 5.49 (br d, 1H), 4.29 (m 1H), 3.46 (d, 2H), 3.37(s, 3H), 1.29 (d, 3H). 71 δ 8.41 (d, 1H), 8.36 (d, 1H), 7.57 (s, 1H),7.30 (m, 4H), 7.09 (d, 1H), 6.97 (d, 1H), 6.73 (t, 1H), 5.92 (br s, 1H),4.65 (m 1H), 3.99 (m, 2H), 3.87 (m, 1H), 3.79 (m, 1H), 2.33 (m, 1H),1.93 (m, 1H). 72 δ 8.41 (d, 1H), 8.36 (d, 1H), 7.56 (s, 1H), 7.51 (s,1H), 7.23 (m, 4H), 7.01 (m, 1H), 6.97 (d, 1H), 5.90 (br s, 1H), 4.67 (m1H), 3.99 (m, 2H), 3.87 (m, 1H), 3.79 (m, 1H), 2.33 (m, 1H), 1.93 (m,1H). 73 δ 8.39 (d, 1H), 8.32 (d, 1H), 7.33 (d, 1H), 7.21 (s, 1H), 6.99(m, 2H), 6.95 (d, 1H), 6.45 (s, 1H), 5.19 (d, 1H), 4.11 (m, 1H), 4.02(m, 2H), 3.53 (t, 2H), 2.05 (m, 2H), 1.55 (m, 2H). 74 δ 8.41 (d, 1H),8.36 (d, 1H), 7.57 (s, 1H), 7.30 (m, 4H), 7.09 (d, 1H), 6.97 (d, 1H),6.73 (t, 1H), 5.92 (br s, 1H), 4.65 (m 1H), 3.99 (m, 2H), 3.87 (m, 1H),3.79 (m, 1H), 2.33 (m, 1H), 1.93 (m, 1H). 75 δ 8.38 (d, 1H), 8.34 (d,1H), 7.54 (s, 2H), 7.32 (d, 1H), 7.25 (m, 2H), 7.11 (d, 1H), 6.93 (d,1H), 6.73 (t, 1H), 5.82 (br s, 1H), 4.15 (m, 1H), 4.02 (d, 1H), 3.75 (m,1H), 3.61 (m, 1H), 3.46 (m 1H), 2.00 (m, 1H), 1.82 (m, 1H), 1.68 (m,2H). 77 δ 8.30 (d, 1H), 8.23 (d, 1H), 7.16 (m, 4H), 6.78 (d, 1H), 6.63(s, 1H), 6.45 (s, 1H), 5.43 (d, 1H), 4.24 (m, 1H), 3.42 (d, 2H), 3.36(s, 3H), 2.25 (s, 6H), 1.24 (d, 2H). 78 8.33 (d, 1H), 8.30 (d, 1H), 7.43(s, 1H), 7.42 (d, 2H), 7.15 (d, 1H), 6.97 (s, 1H), 6.86 (d, 1H), 6.85(s, 1H), 5.52 (d, 1H), 4.27 (m, 1H), 3.46 (d, 2H), 3.36 (s, 3H), 1.27(d, 2H). 79 8.34 (d, 1H), 8.29 (d, 1H), 7.30 (m, 2H), 7.12 (m, 3H), 6.96(s, 1H), 6.89 (d, 1H), 5.62 (d, 1H), 4.27 (m, 1H), 3.46 (d, 2H), 3.36(s, 3H), 1.27 (d, 2H). 80 δ 8.34 (d, 1H), 8.31 (d, 1H), 7.37 (d, 1H),7.16 (m, 3H), 6.88 (d, 1H), 6.81 (s, 1H), 6.49 (s, 1H), 5.18 (d, 1H),4.05 (m, 1H), 3.97 (m, 2H), 3.47 (t, 2H), 2.30 (s, 3H), 2.00 (m, 2H),1.52 (m, 2H). 81 δ 8.35 (d, 1H), 8.31 (d, 1H), 7.44 (d, 2H), 7.28 (m,1H), 7.16 (t, 1H), 6.95 (s, 2H), 6.91 (d, 1H), 5.43 (d, 1H), 4.05 (m,1H), 3.97 (m, 2H), 3.47 (t, 2H), 2.00 (m, 2H), 1.52 (m, 2H). 85 δ 8.32(d, 1H), 8.25 (d, 1H), 7.21 (d, 1H), 7.15 (t, 1H), 6.92 (d, 1H), 6.81(m, 3H), 6.46 (s, 1H), 5.39 (d, 1H), 4.25 (m, 1H), 3.78 (s, 3H), 3.44(m, 2H), 3.36 (s, 3H), 2.26 (s, 3H), 1.28 (d, 3H). 86 δ 8.23 (d, 1H),8.19 (d, 1H), 8.04 (m, 1H), 7.86 (m, 1H), 7.75 (d, 1H), 7.43 (m, 3H),7.30 (s, 1H), 7.17 (d, 1H), 6.65 (d, 1H), 6.56 (s, 1H), 5.46 (br s, 1H),4.06 (m, 1H), 3.34 (m, 2H), 3.29 (s, 3H), 2.44 (s, 3H), 1.13 (d, 3H). 87δ 8.33 (d, 1H), 8.27 (d, 1H), 7.22 (d, 1H), 7.17 (s, 1H), 7.02 (s, 1H),6.84 (d, 1H), 6.78 (s, 1H), 6.48 (s, 1H), 5.41 (d, 1H), 4.25 (m, 1H),3.44 (d, 2H), 3.37 (s, 3H), 2.33 (s, 3H), 2.25 (s, 3H), 1.25 (d, 3H). 88δ 8.32 (d, 1H), 8.26 (d, 1H), 7.17 (m, 2H), 6.92 (d, 1H), 6.84 (m, 3H),6.55 (s, 1H), 5.36 (s, 1H), 4.05 (m, 1H), 3.98 (m, 2H), 3.78 (s, 3H),3.49 (t, 2H), 2.26 (s, 3H), 1.98 (m, 2H), 1.52 (m, 2H). 89 δ 8.25 (d,1H), 8.19 (d, 1H), 8.05 (m, 1H), 7.87 (m, 1H), 7.78 (d, 1H), 7.46 (m,3H), 7.38 (s, 1H), 7.13 (d, 1H), 6.71 (d, 1H), 6.57 (s, 1H), 5.42 (s,1H), 4.06 (m, 1H), 3.90 (m, 3H), 3.33 (m, 2H), 2.43 (s, 3H), 1.83 (m,2H), 1.42 (m, 2H). 90 δ 8.33 (d, 1H), 8.27 (d, 1H), 7.19 (m, 2H), 7.02(s, 1H), 6.87 (d, 1H), 6.78 (s, 1H), 6.61 (s, 1H), 5.35 (d, 1H), 4.00(m, 3H), 3.48 (t, 2H), 2.33 (s, 3H), 2.25 (s, 3H), 1.99 (m, 2H), 1.56(m, 2H). 91 δ 8.37 (d, 1H), 8.30 (d, 1H), 7.41 (m, 2H), 7.26 (m, 1H),7.16 (t, 1H), 6.89 (d, 1H), 6.73 (m, 2H), 5.63 (d, 1H), 4.31 (m 1H),3.47 (d, 2H), 3.37 (s, 3H), 2.25 (s, 3H), 1.29 (d, 3H). 92 δ 8.30 (d,1H), 8.23 (d, 1H), 7.27 (d, 1H), 7.19 (d, 1H), 7.10 (d, 1H), 6.82 (m,2H), 6.66 (s, 1H), 5.55 (d, 1H), 4.22 (m 1H), 3.44 (d, 2H), 3.35 (s,3H), 2.32 (s, 3H), 2.23 (s, 3H), 1.25 (d, 3H). 93 δ 8.35 (d, 1H), 8.26(d, 1H), 7.36 (m, 1H), 7.24 (m, 1H), 7.22 (s, 1H), 6.86 (d, 2H), 6.72(s, 1H), 5.54 (d, 1H), 4.26 (m 1H), 3.46 (d, 2H), 3.37 (s, 3H), 2.25 (s,3H), 1.29 (d, 3H). 97 δ 8.34 (d, 1H), 8.27 (d, 1H), 7.71 (m, 2H), 7.37(m, 1H), 7.31 (d, 1H), 6.92 (s, 1H), 6.85 (d, 1H), 6.61 (s, 2H), 5.44(d, 1H), 4.25 (m 1H), 3.45 (m, 2H), 3.37 (s, 3H), 1.27 (d, 3H). 98 δ8.35 (d, 1H), 8.29 (d, 1H), 7.72 (m, 2H), 7.39 (t, 1H), 7.29 (d, 1H),6.90 (s, 1H), 6.89 (d, 1H), 6.53 (s, 2H), 5.17 (d, 1H), 4.00 (m, 3H),3.50 (t, 2H), 2.03 (m, 2H), 1.57 (m, 2H). 99 δ 8.37 (d, 1H), 8.32 (d,1H), 7.45 (s, 2H), 7.30 (d, 1H), 6.97 (s, 1H), 6.92 (d, 1H), 6.72 (s,1H), 5.32 (d, 1H), 4.00 (m, 3H), 3.53 (t, 2H), 2.05 (m, 2H), 1.57 (m,2H). 100 δ 8.36 (d, 1H), 8.28 (d, 1H), 7.38 (s, 1H), 7.23 (m, 2H), 6.89(d, 1H), 6.83 (s, 1H), 6.51 (s, 1H), 5.24 (d, 1H), 4.00 (m, 3H), 3.53(t, 2H), 2.31 (s, 3H), 2.01 (m, 2H), 1.57 (m, 2H). ^(a1)H NMR data arein ppm downfield from tetramethylsilane. Couplings are designated by(s)—singlet, (d)—doublet, (t)—triplet, (q)—quartet, (dd)—doublet ofdoublets, (dt)—doublet of triplets, (br s)—broad singlet, (m)—multiplet.

Biological Examples of the Invention

General protocol for preparing test suspensions for Tests A-R: The testcompounds were first dissolved in acetone in an amount equal to 3% ofthe final volume and then suspended at the desired concentration (inppm) in acetone and purified water (50/50 mix) containing 250 ppm of thesurfactant Trem® 014 (polyhydric alcohol esters). The resulting testsuspensions were then used in tests A-R. In Tests A-M, compounds weresprayed as a 200 ppm test suspension (equivalent to a rate of 500 g/ha)or as a 40 ppm test suspension to the point of runoff on the testplants. In Tests N-R, compounds were sprayed as a 100 g/ha testsuspension (equivalent to a rate of 100 ppm) on the test plants at anapplication volume of 1000 L/ha.

Test A

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporedust of Erysiphe graminis f. sp. tritici (the causal agent of wheatpowdery mildew) and incubated in a growth chamber at 20° C. for 8 days,after which time disease ratings were made.

Test B

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporesuspension of Puccinia recondita f. sp. tritici (the causal agent ofwheat leaf rust) and incubated in a saturated atmosphere at 20° C. for24 h, and then moved to a growth chamber at 20° C. for 7 days, afterwhich time disease ratings were made.

Test C

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporesuspension of Septoria nodorum (the causal agent of wheat glume blotch)and incubated in a saturated atmosphere at 20° C. for 48 h, and thenmoved to a growth chamber at 20° C. for 7 days, after which time diseaseratings were made.

Test D

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporesuspension of Septoria tritici (the causal agent of wheat leaf blotch)and incubated in saturated atmosphere at 20° C. for 48 h, and moved to agrowth chamber at 20° C. for 19 additional days, after which timedisease ratings were made.

Test E

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporesuspension of Fusarium graminearum (the causal agent of wheat head scab)and incubated in a saturated atmosphere at 20° C. for 72 h, and thenmoved to a growth chamber at 20° C. for 5 days, after which time diseaseratings were made.

Test F

The test suspension was sprayed to the point of run-off on tomatoseedlings. The following day the seedlings were inoculated with a sporesuspension of Botrytis cinerea (the causal agent of tomato Botrytis) andincubated in saturated atmosphere at 20° C. for 48 h, and then moved toa growth chamber at 24° C. for 3 additional days, after which timedisease ratings were made.

Test G

The test suspension was sprayed to the point of run-off on cucumberseedlings. The following day the seedlings were inoculated with a sporesuspension of Sclerotinia sclerotiorum (the causal agent of cucumberwhite mold) and incubated in saturated atmosphere at 24° C. for 72 h,and then moved to a growth chamber at 24° C. for 3 additional days,after which time disease ratings were made.

Test H

The test suspension was sprayed to the point of run-off on wheatseedlings. The following day the seedlings were inoculated with a sporesuspension of Alternaria solani (the causal agent of tomato earlyblight) and incubated in a saturated atmosphere at 27° C. for 48 h, andthen moved to a growth chamber at 20° C. for 5 days, after which timedisease ratings were made.

Test I

The test suspension was sprayed to the point of run-off on cucumberseedlings. The following day the seedlings were inoculated with a sporesuspension of Colletotrichum orbiculare (the causal agent of cucumberColletotrichum anthracnose) and incubated in saturated atmosphere at 20°C. for 24 h, and moved to a growth chamber at 24° C. for 5 additionaldays, after which time disease ratings were made.

Test J

The test suspension was sprayed to the point of run-off on creeping bentgrass seedlings. The following day the seedlings were inoculated with ablended mix of wheat bran and mycelium of Rhizoctonia oryzae (the causalagent of turf brown patch) and incubated in a saturated atmosphere at27° C. for 48 h, and then moved to a growth chamber at 27° C. for 3days, after which time disease ratings were made.

Test K

The test suspension was sprayed to the point of run-off on tomatoseedlings. The following day the seedlings were inoculated with a sporesuspension of Phytophthora infestans (the causal agent of tomato lateblight) and incubated in a saturated atmosphere at 20° C. for 24 h, andthen moved to a growth chamber at 20° C. for 4 days, after which timedisease ratings were made.

Test L

Grape seedlings were inoculated with a spore suspension of Plasmoparaviticola (the causal agent of grape downy mildew) and incubated in asaturated atmosphere at 20° C. for 24 h. After a short drying period,the test suspension was sprayed to the point of run-off on the grapeseedlings and then moved to a growth chamber at 20° C. for 6 days, afterwhich time the test units were placed back into a saturated atmosphereat 20° C. for 24 h. Upon removal, disease ratings were made.

Test M

The test suspension was sprayed to the point of run-off on bluegrassseedlings. The following day the seedlings were inoculated with a sporesuspension of Pythium aphanidermatum (the causal agent of bluegrasspythium blight) and incubated in a covered containers to providesaturated atmosphere at 27° C. for 48 h, and then the covers wereremoved and the plants left at 27° C. for 3 additional days, after whichtime disease ratings were made.

Test N

The test suspension was sprayed on grape seedlings. The following daythe seedlings were inoculated with a spore suspension of Uncinulanecator (the causal agent of grape powdery mildew) and incubated in agreenhouse or growth chamber at 24° C. for 10-12 days, after which timedisease ratings were made.

Test O

The test suspension was sprayed on apple seedlings. The following daythe seedlings were inoculated with a spore suspension of Venturiainaequalis (the causal agent of apple scab) and incubated in a saturatedatmosphere at 20° C. for 48 h, and then moved to a growth chamber at 22°C. for 12 days, after which time disease ratings were made.

Test P

The test suspension was sprayed on rice seedlings. The following day theseedlings were inoculated with a blended mix of wheat bran and myceliumof Rhizoctonia oryzae (the causal agent of rice sheath blight) andincubated in saturated atmosphere at 27° C. for 48 h, and moved to agrowth chamber at 27° C. for 5 additional days, after which time diseaseratings were made.

Test Q

The test suspension was sprayed on rice seedlings. The following day theseedlings were inoculated with a spore suspension of Magnaporthe grisea(the causal agent of rice blast) and incubated in a saturated atmosphereat 24° C. for 24 h, and then moved to a growth chamber at 27° C. for 7days, after which time disease ratings were made.

Test R

The test suspension was sprayed on grape seedlings. The following daythe seedlings were inoculated with a spore suspension of Plasmoparaviticola (the causal agent of grape downy mildew) and incubated in asaturated atmosphere at 20° C. for 24 h, then moved to a growth chamberat 20° C. for 7 days, after which time the test units were placed backinto a saturated atmosphere at 20° C. for 24 h. Upon removal, diseaseratings were made.

Results for Tests A-M are given in Table A1. In the table, a rating of100 indicates 100% disease control and a rating of 0 indicates nodisease control (relative to the controls). A dash (-) indicates no testresults. All results are for 200 ppm except where followed by “*” whichindicates 40 ppm.

TABLE A1 Cmpd No. Test A Test B Test C Test D Test E Test F Test G TestH Test I Test J Test K Test L Test M 1 76 96 100   0 98 98 — — 99 — — —— 2 94 99 99 71 95 93 — 97 99 — — — — 3 64 96 100  67 27  0 — — 94 — — —— 4  0 91 99 11  0  0 — — 66 — — — — 5 — 100  100  98 98 80 —  0 99 — —— — 6 — 97 100  58 84 85 — 98 0 — — — — 7 — 99 100  87  0  0 —  0 96 — —— — 8 — 97 95 42 77  0 — 41 0 — — — — 9 — 100  99 20 80 73 — 99 100 — —— — 10 — 93 100  10 61  0 — 97 99 — — — — 11 — 96 100   0 99 96 — 98 — —— — — 12 — 79 100   0 96 37 — 98 — — — — — 13 — 100  100  26 96 87 — 98* — — — — — 14 — 79 100   0 92 55 — 95 — — — — — 15 — 32 92  0  0  0— 90 93 — — — — 16 — 99 99 71 99 96 — 98 97 — — — — 17 — 86 99 66  0 97— 90 98 — — — — 18 — 100  100  0 85 95 —  89* 99 — — — — 19 — 97 100  8797 99 — 93 99 — — — — 20 — 74 100  20 91 99 — 96 0 — — — — 21 — 99 97 1387 72 — — 96 — — — — 22  69* 99 100  36 99  99* — 100* 100 — — — — 23 0* 98 100  13 98 90 — 100* 99 — — — — 24 — 97 100  24 99 70 — 100  — —— — — 25 — 99 100  16 99 63 — 99 — — — — — 26 — 98 100   2 98 17 — 91 —— — — — 27  0 100  99 75 97 94 — 100* — — — — — 28 — 73 99  0 90  84* —85 96 — — — — 29 — 100  100  90 99 91 —  97* — — — — — 30 67 99 100  8891 96 —  87* — — — — — 31  0 100  100  88 89 99 — 92 — — — — — 32  0 99100  39 38 94 — 99 — — — — — 33  0 87 99 22  83*  0 — 94 — — — — — 34  098 100  59 68  0 — 94 — — — — — 35 72 100  98  7 98 91 — — — — — — — 36 0*  99* 100*  29*  91*  99* —  99* — — — — — 37 79 99 98  0 41  0 — 72— — — — — 38  0 98 100   0 65 13 — 93 — — — — — 39  0*  98*  99*  24* 82*  60* —  99* — — — — — 40 63 90 99 27 48 99 83 — 84 0 0 0 0 41 57 9899 15 45 96 94 — 54 34  0 0 0 42  0 88 94  9  0 75 — — 92 0 0 16  0 4329 99 99 — 100  92 — — 90 9 0 0 0 44  0 89 98 — 99  0 — — 40 0 0 0 0 4577 79 98 — 90 20 — — 8 0 0 0 0 46  0 91 97 — 94 7 — — 0 0 0 0 0 47  0 85 0 — 92  0 — — 40 0 0 0 0 48  0 99 87 —  0 15 — — 26 0 0 0 0 49 86 99 92— 81 90 — — 67 0 0 0 0 50  0 99 84 — 72 94 — — 96 0 0 0 0 51 88 99 98 —48 99 — — 92 0 0 0 0 52  0 94 90 31  0 98 — — 0 — — — — 53 88 98 96 41 0 99 — — 26 — — — — 54  0 96 64 35  0 85 — — 0 — — — — 55  0 95 78 20 0  0 — — 0 — — — — 56 84 99 99 82 90 99 — — 90 — — — — 57  0 95 51  9 0  0 — — 0 — — — — 58 44 98 99 36  0 86 — — 24 — — — — 59 87 — 99  0  057 — — 0 — — — — 60 97 95 100  18  0 61 — — 0 — — — — 61  0 96 99 32  0 0 — — 0 — — — — 62  0 94  0 14  0  0 — — 0 — — — — 63  0 80  0 41  0  0— — 90 — — — — 64  0 94 97 95  0  0 — — 92 — — — — 65 46 80 96  0  0  0— — 83 — — — — 66  0 85 99 92 64 84 — — — — — — — 67 17 97 99 52  0 95 —— 79 — — — — 68  0 95 99 96  0 93 — — — — — — — 69 91 94 97 77  0 85 — —0 — — — — 70 95 98 99 17 84 97 — — 98 — — — — 71  0 94 99 25  0 77 — —46 — — — — 72  0 80 95 11  0  0 — — 0 — — — — 73 43 96 99 40  0 57 — —85 — 0 — 0 74  0 94 99 72  0 48 — — 17 — — — — 75  0 83 89 28  0 90 — —9 — — — — 76 36 99 99 87 93 97 — — 72 — — — — 77 95 99 99 61 92 88 — —96 — — — — 78 39 99 99 60  0 93 — — 98 — — — — 79  0 99 99 5  0 94 — —96 — — — — 80 86 100  99 93 98 99 — — 98 — — — — 81 95 100  99 92 97 99— — 91 — — — — 82  0 98 91 68  0  0 — — 29 — — — — 83  0 95 99 92  0 53— — 0 — — — — 84 28 91 99 59  0 99 — — 0 — — — — 85 56 94 99  0  0 93 —— 96 — — — — 86 27 55 94  0  0 96 — — 0 — — — — 87 87 95 100  49  0 96 —— 88 — — — — 88 99 100  97  0 91  0 — — 0 — — — — 89 74 95 100   0 89 99— — 0 — — — — 90 98 99 100  47 100  99 — — 93 — — — — 91 97 99 94  7 1998 — — 0 — — — — 92 91 94 100  65  0 99 — — 0 — — — — 93 84 99 100  7866 98 — — 0 — — — — 94 — 89 95 69  0 72 —  0 0 — — — — 95 — 88 94 77  0 0 —  0 0 — — — — 96 — 85 99 28  0 86 —  0 0 — — — — 97  0 97 100  67 4899 — — 93 — — — — 98 89 99 99 83 97 91 — — 0 — — — — 99  0 95 100  30 92 0 — — 0 — — — — 100  0 98 98 77 96  0 — 99 0 — — — — 101 — 99 100  5397 99 — 92 97 — — — — 102 — 93 100   3 27 83 — 41 0 — — — — 103 — 97100   1  0  0 — 99 0 — — — — 104 — 99 94 10  0  0 —  0 0 — — — — 105  097 92 — 73 78 — — 0 0 0 0 0 106 24 94 99 17 32 85 — — 37 0 0 0 0 107  094 100   8 89 28 — — 72 0 0 0 0 108  0 80 0 — 98 38 — — 0 0 0 0 0 109  096 94  5  0  0 — — 9 — — — — 110 — 89 60  9  0 65 — 89 97 — — — —

Results for Tests N-R are given in Table A2. In the table, a rating of100 indicates 100% disease control and a rating of 0 indicates nodisease control (relative to the controls). A dash (-) indicates no testresults. All results are for 100 ppm.

TABLE A2 Cmpd. No. Test N Test O Test P Test Q Test R 1 90 78 — — 26 289 95 100  93 60 11 85 92 — — 27 16 99 76 — — 40 18 99 83 100 100 86 1995 33 — — 73 21 57 99 — — 79 22 99 99 100 100 83 23 61 99 — — 30 25 9959 — — 86 26 69 96 — — 96 56 64 75 100  98 97 67 55 73 — — 94 81 97 69 —— 97 90 98 — — — 98 99 30 83 — — 99

1. A compound selected from Formula 1, or an N-oxide or salt thereof,

wherein R¹ is H, halogen, cyano, hydroxy, amino, nitro, —CHO or—C(═O)NH₂; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₂-C₈alkylcarbonyl, C₂-C₈ alkoxycarbonyl, C₂-C₈ alkylaminocarbonyl, C₃-C₁₀dialkylaminocarbonyl, C₁-C₆ alkoxy, C₃-C₈ cycloalkoxy, C₂-C₈alkylcarbonyloxy, C₄-C₁₀ cycloalkylcarbonyloxy, C₁-C₆ alkylthio, C₃-C₈cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₃-C₈cycloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₃-C₈cycloalkylamino, C₂-C₈ alkylcarbonylamino, C₁-C₆ alkylsulfonylamino,G^(A), G^(N) or naphthalenyl, each optionally substituted with one ormore substituents selected from the group consisting of halogen, cyano,hydroxy, amino, nitro, —CHO, —C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₈ alkylcarbonyl, C₂-C₈haloalkylcarbonyl, C₄-C₁₀ cycloalkylcarbonyl, C₂-C₈ alkoxycarbonyl,C₄-C₁₀ cycloalkoxycarbonyl, C₂-C₈ alkylaminocarbonyl, C₃-C₁₀dialkylaminocarbonyl, C₄-C₁₀ cycloalkylaminocarbonyl, C₁-C₆ alkoxy,C₁-C₆ haloalkoxy, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy, C₄-C₁₀cycloalkylalkoxy, C₂-C₆ alkenyloxy, C₂-C₆ haloalkenyloxy, C₂-C₆alkynyloxy, C₃-C₆ haloalkynyloxy, C₂-C₈ alkoxyalkoxy, C₂-C₈alkylcarbonyloxy, C₂-C₈ haloalkylcarbonyloxy, C₄-C₁₀cycloalkylcarbonyloxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₃-C₈cycloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, C₃-C₁₀trialkylsilyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₁-C₆haloalkylamino, C₂-C₈ halodialkylamino, C₃-C₈ cycloalkylamino, C₂-C₈alkylcarbonylamino, C₂-C₈ haloalkylcarbonylamino, C₁-C₆alkylsulfonylamino, C₁-C₆ haloalkylsulfonylamino, G^(A), G^(N) andphenyl; R² is H, cyano, hydroxy, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆ haloalkynyl, C₃-C₈cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀ alkylcycloalkyl, C₄-C₁₀cycloalkylalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₂-C₈ alkoxyalkyl, C₄-C₁₀cycloalkoxyalkyl or C₃-C₁₀ alkoxyalkoxyalkyl; or R¹ and R² are takentogether with the nitrogen to which they are attached to form a 3- to7-membered ring, containing ring members in addition to the nitrogenselected from the group consisting of C(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—,—C(R⁸)═N—, —N═N—, C(═O), C(═S), C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) andSiR^(5a)R^(5b); each G^(A) is independently a benzoyl, phenoxy orphenylsulfonyl or a 5- or 6-membered heteroaromatic ring; each G^(N) isindependently a 3- to 7-membered nonaromatic carbocyclic or heterocyclicring, containing ring members selected from the group consisting ofC(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)—N—, —N═N—, C(═O), C(═S),C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b); each R³ isindependently H, cyano, hydroxy, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₂-C₆ haloalkynyl,C₃-C₈ cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀ alkylcycloalkyl, C₄-C₁₀cycloalkylalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₃-C₈ cycloalkenyl, C₂-C₈alkoxyalkyl, C₄-C₁₀ cycloalkoxyalkyl, C₃-C₁₀ alkoxyalkoxyalkyl, C₂-C₈alkylthioalkyl, C₂-C₈ alkylsulfinylalkyl, C₂-C₈ alkylsulfonylalkyl,C₂-C₈ alkylaminoalkyl, C₄-C₁₀ dialkylaminoalkyl, C₃-C₈haloalkylaminoalkyl, C₄-C₁₀ cycloalkylaminoalkyl, C₂-C₁₀ alkylcarbonyl,C₂-C₁₀ haloalkylcarbonyl, C₄-C₁₀ cycloalkylcarbonyl, C₂-C₁₀alkoxycarbonyl, C₄-C₁₀ cycloalkoxycarbonyl, C₂-C₁₀ alkylaminocarbonyl,C₃-C₁₀ dialkylaminocarbonyl, C₄-C₁₀ cycloalkylaminocarbonyl, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, C₃-C₈ cycloalkoxy, C₃-C₈ halocycloalkoxy,C₄-C₁₀ cycloalkylalkoxy, C₂-C₈ alkoxyalkoxy, C₁-C₆ alkylthio, C₁-C₆haloalkylthio, C₃-C₈ cycloalkylthio, C₁-C₆ alkylsulfonyl, C₁-C₆haloalkylsulfonyl, C₃-C₈ cycloalkylsulfonyl, C₃-C₅ trialkylsilyl orC₃-C₅ halotrialkylsilyl; each R⁴ is independently H, cyano, amino,hydroxy, C₁-C₆ alkyl, C₃-C₁₀ cycloalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆haloalkylcarbonyl, C₁-C₆ alkoxy, phenyl or benzoyl; each R^(5a) andR^(5b) is independently C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈cycloalkyl, C₃-C₈ halocycloalkyl, C₄-C₁₀ cycloalkylalkyl, C₄-C₁₀alkylcycloalkyl, C₅-C₁₂ alkylcycloalkylalkyl, C₁-C₆ haloalkyl, C₁-C₆alkoxy or C₁-C₆ haloalkoxy; G is benzoyl, phenoxy, phenylethynyl,phenylsulfonyl or —(CR^(6a)R^(6b))_(n)G^(B); G^(B) is a phenyl ring,naphthalenyl or 5- to 6-membered heteroaromatic ring, each ringoptionally substituted with 1 to 5 substituents independently selectedfrom R⁷; each R^(6a) and R^(6b) is independently H, halogen, —C(═O)OH,C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₃-C₈halocycloalkyl, C₄-C₁₀ cycloalkylalkyl, C₄-C₈ alkylcycloalkyl, C₅-C₁₂alkylcycloalkylalkyl, C₁-C₆ haloalkyl, C₂-C₈ alkoxycarbonyl, C₁-C₆alkoxy or C₁-C₆ haloalkoxy; or R^(6a) and R^(6b) in geminalconfiguration are taken together with the carbon atom to which they areattached to form a 3- to 7-membered ring, containing ring members inaddition to the carbon atom selected from the group consisting ofC(R⁸)₂, O, S, NR³, —C(R⁸)═C(CR⁸)—, —C(R⁸)═N—, —N═N—, C(═O), C(═S),C(═NR⁴), S(═O)_(p)(═NR⁴)_(q) and SiR^(5a)R^(5b); R⁷ is halogen, cyano,hydroxy, amino, nitro, —CHO, —C(═O)OH, —C(═O)NH₂, —SO₂NH₂, C₁-C₆ alkyl,C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ haloalkyl, C₂-C₈ alkylcarbonyl,C₂-C₈ haloalkylcarbonyl, C₂-C₈ alkoxycarbonyl, C₄-C₁₀cycloalkoxycarbonyl, C₅-C₁₂ cycloalkylalkoxycarbonyl, C₂-C₈alkylaminocarbonyl, C₃-C₁₀ dialkylaminocarbonyl, C₁-C₆ alkoxy, C₁-C₆haloalkoxy, C₂-C₈ alkylcarbonyloxy, C₁-C₆ alkylthio, C₁-C₆haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylaminosulfonyl, C₂-C₈dialkylaminosulfonyl, C₃-C₁₀ trialkylsilyl, C₁-C₆ alkylamino, C₂-C₈dialkylamino, C₂-C₈ alkylcarbonylamino, C₁-C₆ alkylsulfonylamino,phenyl, pyridinyl or thienyl; each R⁸ is independently H, halogen, CN,C₁-C₃ alkyl or C₁-C₃ alkoxy; X is N or CR^(9c); Y is N or CR^(9d); W isN; Z is N; each R^(9a), R^(9b), R^(9c), R^(9d), R^(9e) and R^(9f) isindependently H, halogen, nitro, CN, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆cycloalkyl, C₁-C₃ alkoxy or C₁-C₃ haloalkoxy; n is an integer selectedfrom 0 through 6; and p and q are independently 0, 1 or 2 in eachinstance of S(═O)_(p)(═NR⁴)_(q), provided that the sum of p and q is 0,1 or 2; provided that: (a) when R¹ is hydroxy, then R² is other thanhydroxy; and (b) at least one of X or Y is N.
 2. A compound of claim 1wherein R¹ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl or G^(N), eachoptionally substituted with one or more substituents selected from thegroup consisting of halogen, cyano, hydroxy, amino, nitro, —CHO,—C(═O)OH, —C(═O)NH₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₈ cycloalkoxy, C₃-C₈halocycloalkoxy, C₄-C₁₀ cycloalkylalkoxy, C₂-C₆ alkenyloxy, C₂-C₆haloalkenyloxy, C₂-C₆ alkynyloxy, C₃-C₆ haloalkynyloxy, C₂-C₈alkoxyalkoxy and G^(N); R² is H or C₁-C₆ alkyl; G is G^(B); X is N; andY is CH.
 3. A compound of claim 2 wherein R¹ is 2-methoxy-1-methylethyl,2-ethoxy-1-methylethyl, 2-methoxy-1-ethylethyl, 2-ethoxy-1-ethylethyl,3-methoxy-1-methylpropyl, 3-ethoxy-1-methylpropyl,1-ethyl-3-methoxypropyl, 3-ethoxy-1-ethylpropyl ortetrahydro-2H-pyran-4-yl; R² is H; and G^(B) is naphthalenyl or a phenylor pyridinyl ring, each optionally substituted with up to 3 substituentsindependently selected from halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl andC₁-C₆ alkoxy.
 4. A compound of claim 3 wherein R¹ is2-methoxy-1-methylethyl or tetrahydro-2H-pyran-4-yl; and G^(B) is phenyloptionally substituted at the 3 and 5 positions with halogen.
 5. Acompound of claim 4 wherein G^(B) is phenyl optionally substituted atthe 3 position with halogen.
 6. A method for controlling plant diseasescaused by Ascomycete or Basidiomycete fungal plant pathogens comprisingapplying to the plant or portion thereof, or to the plant seed orseedling, a fungicidally effective amount of a compound of claim
 1. 7. Afungicidal composition comprising (a) a fungicidally effective amount ofa compound of claim 1; and (b) a fungicidally effective amount of atleast one other fungicide.
 8. A fungicidal composition comprising (1) afungicidally effective amount of a compound of claim 1; and (2) at leastone additional component selected from the group consisting ofsurfactants, solid diluents and liquid diluents.
 9. A compound selectedfrom the group consisting of:N-(3,5-difluorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;N-(3-fluorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;andN-(3-fluorophenyl)-4-[2-[2-methoxy-1-methylethyl)amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine.10. A compound selected from the group consisting of:N-(3-chlorophenyl)-4-[2-[(2-methoxy-1-methylethyl)amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;N-(3-chlorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine;3-[[4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-yl]amino]benzonitrile;4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-N-(3-methylphenyl)-1,3,5-triazin-2-amine;andN-(3-chloro-4-fluorophenyl)-4-[2-[[(1S)-2-methoxy-1-methylethyl]amino]-4-pyrimidinyl]-1,3,5-triazin-2-amine.